Biomedical subjects

F A Hopp

Publications and source records attributed to F A Hopp.

At least 37 records · Page 2Linked to original sources

PubMed1997

Modulation of the synaptic drive to respiratory premotor and motor neurons.

The characteristics of GABAergic inhibitory modulation of respiratory bulbospinal neuronal activity and short-term potentiation (STP) of phrenic motoneuronal activity were studied. Extracellular unit recording and picoejection techniques in anesthetized dogs showed that both the spontaneous rhythmic and reflexly induced discharge patterns of inspiratory (I) and expiratory (E) premotor neurons were proportionately amplified by the localized application of picomole amounts of bicuculline (Bic), a competitive GABAA antagonist. Intracellular recording and paired-pulse stimulation techniques in anesthetized rats demonstrated an STP of phrenic motor output that appears to be mediated by NMDA receptors and is associated with facilitation of EPSPs and prolonged depolarization of individual phrenic motoneurons. We speculate that both GABAergic gain modulation of premotor neuronal activity and NMDA-mediated STP of phrenic activity may be neural substrates which are involved with the optimization of respiratory and non-respiratory behaviors, via adaptive and/or differential control of breathing.

Action Potentials↗

PubMed1997

Dose-dependent effects of halothane on the phrenic nerve responses to acute hypoxia in vagotomized dogs.

BACKGROUND: Previous studies in dogs and humans suggest that the carotid body chemoreceptor response to hypoxia is selectively impaired by halothane. The present studies in an open-loop canine preparation were performed to better delineate the effects of anesthetic concentrations of halothane on the carotid body chemoreceptor-mediated phrenic nerve response to an acute hypoxic stimulus. METHODS: Three protocols were performed to study the effects of halothane anesthesia on the phrenic nerve response to 1 min of isocapnic hypoxia (partial pressure of oxygen [PaO2] at peak hypoxia, 35-38 mmHg) in unpremedicated, anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. In protocol 1, the dose-dependent effects of halothane from 0.5-2.0 minimum alveolar concentration (MAC) on the hypoxic response during moderate hypercapnia (partial pressure of carbon dioxide [PaCO2], 60-65 mmHg) were studied in 10 animals. In protocol 2, the hypoxic responses at 1 MAC halothane near normocapnia (PaCO2, 40-45 mmHg) and during moderate hypercapnia were compared in an additional four animals. In protocol 3, the hypoxic response of 4 of 10 dogs from protocol 1 was also studied under sodium thiopental (STP) anesthesia after they completed protocol 1. RESULTS: Protocol 1: Peak phrenic nerve activity (PPA) increased significantly during the hypoxic runs compared with the isocapnic hyperoxic controls at all halothane doses. The phrenic nerve response to the hypoxic stimulus was present even at the 2 MAC dose. Protocol 2: The net hypoxic responses for the two carbon dioxide background levels at 1 MAC were not significantly different. Protocol 3: The net hypoxic response of PPA for the STP anesthetic was not significantly different from the 1 MAC halothane dose. Bilateral carotid sinus denervation abolished the PPA response to hypoxia. CONCLUSIONS: The phrenic nerve response to an acute, moderately severe isocapnic hypoxic stimulus is dose-dependently depressed but not abolished by surgical doses of halothane. This analysis does not suggest a selective depression of the carotid body chemoreceptor response by halothane. The observed hypoxic phrenic response was mediated by the carotid body chemoreceptors in vagotomized dogs because bilateral carotid sinus denervation abolished all increases in PPA.

Anesthetics, Inhalation↗

PubMed1997

Effects of halothane on the phrenic nerve responses to carbon dioxide mediated by carotid body chemoreceptors in vagotomized dogs.

BACKGROUND: Previous studies in dogs showed that the phrenic nerve response to an acute hypoxic stimulus was dose dependently depressed by 0.5-2.0 minimum alveolar concentration (MAC) of halothane but not abolished. Because a carbon dioxide stimulus is transduced by a different mechanism in the carotid body chemoreceptors (CBCRs) than is a hypoxic stimulus, inhalational anesthetics may preferentially depress one of these transduction processes, the central neuronal processing, or both, of the integrated responses to these two types of inputs. METHODS: Carotid body chemoreceptor stimulation was produced by short (1-1.5 s), bilateral, 100% carbon dioxide in saline infusions into the carotid arteries during neural inspiration in unpremedicated, halothane-anesthetized, paralyzed, vagotomized dogs during constant mechanical ventilation. The phrenic neurogram quantified the neural inspiratory response. Four protocols were performed in the study: (1) the dose-dependent effects of halothane anesthesia (0.5-2.0 MAC) during hyperoxic hypercapnia on phrenic nerve activity, (2) the effects of three background levels of the partial pressure of carbon dioxide (PaCO2) on the magnitude of the carbon dioxide infusion responses at 1 MAC halothane, (3) the effects of anesthetic type on the magnitude of the carbon dioxide infusion response, and (4) the effects of CBCR denervation. RESULTS: Peak phrenic nerve activity (PPA) increased significantly during the carbon dioxide-stimulated phrenic burst in protocols 1-3; after denervation there was no response (protocol 4). Halothane produced a dose-dependent reduction in the PPA of control and carbon dioxide infusion-stimulated phrenic bursts and in the net carbon dioxide response. The net PPA responses for the different PaCO2 background levels were not different but were somewhat larger for sodium thiopental anesthesia than for 1.0 MAC halothane. CONCLUSIONS: The phrenic nerve response to an acute, severe carbon dioxide stimulus was dose dependently depressed by surgical doses of halothane. The observed responses to carbon dioxide infusion were mediated by the CBCRs because they were eliminated by CBCR denervation. These results suggest that the CBCR transduction and central transmission of the carbon dioxide signal in terms of inspiratory excitatory drive are not abolished at surgical levels of halothane anesthesia.

Anesthetics, Inhalation↗

PubMed1995

NMDA receptor-mediated transmission of carotid body chemoreceptor input to expiratory bulbospinal neurones in dogs.

1. This study tested the hypothesis that excitatory amino acid receptors mediate the excitatory response of expiratory bulbospinal neurones to carotid body chemoreceptor inputs. 2. Studies were carried out in thiopental sodium anaesthetized, paralysed, ventilated, vagotomized dogs. 3. Brisk, short-duration chemoreceptor activation was produced by bilateral bolus injections of CO2-saturated saline (PCO2 > 700 mmHg) into the autoperfused carotid arteries. A pressurized-reservoir-solenoid valve system was used to deliver the CO2 bolus injections just prior to the onset of the neural expiratory phase, as determined from the phrenic neurogram, about once per minute. 4. Multibarrelled micropipettes were used to record neuronal unit activity and deliver neurotransmitter agents. Net responses of expiratory bulbospinal neurones to peripheral chemoreceptor activation were determined by subtracting the mean discharge frequencies (Fn) during three control expiratory cycles from the Fn during administration of a CO2 test bolus. The role of excitatory amino acid receptors in mediating this response was determined by comparing the baseline and bolus expiratory neuronal Fn before, during and after the pressure microejection of the NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP5) or the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulphamoyl- benzo(f)quinoxaline (NBQX). Ejection rates of AP5 and NBQX were measured by monitoring the movement of the pipette meniscus. 5. AP5 reduced Fn during both the control and bolus cycles, as well as reducing the change in Fn between control and bolus cycles. NBQX had no effect on either baseline or bolus responses. 6. AP5 did not prevent excitation of expiratory bulbospinal neurones by AMPA. Coadministration of AMPA with AP5 prevented the AP5-mediated decrease in Fn but not the dose-dependent reduction in the CO2 bolus response. 7. Taken together, these data strongly suggest that the carotid chemoreceptor-mediated excitation of expiratory bulbospinal neurones is dependent on NMDA but not non-NMDA glutamate receptors.

2-Amino-5-phosphonovalerate↗

PubMed1995

Discharge patterns of baroreceptor-modulated neurons in the nucleus tractus solitarius.

Activity of baroreceptor-modulated neurons in the nucleus tractus solitarius (NTS) was recorded extracellularly during selective pressure stimulation of carotid baroreceptors, using an isolated carotid sinus preparation in anesthetized dogs. One of two different patterns of activity was recorded from individual baro-sensitive neurons in response to slow ramp increases in carotid sinus pressure. The cause of these two distinct firing patterns is not known but preliminary results indicate that it may be due in part to input from different functional types of baroreceptors. These results suggest that some differentiation in blood pressure control may be encoded in the responses of central baro-sensitive neurons in the NTS.

Anesthesia↗

PubMed1995

Reflex effects of stimulation of sympathetic afferents on the triangularis sterni.

The purpose of this study was to determine whether contralateral inhibition of the triangularis sterni is produced by stimulation of intrathoracic sympathetic afferents. Dogs were anesthetized with sodium pentobarbital and placed on positive pressure ventilation. The chest was opened through a mid-sternal incision. Diaphragm and left and right triangularis sterni EMGs were recorded, post-vagotomy, before and during electrical stimulation of the left ventral ansa subclavia (VA), vagosympathetic trunk, ventrolateral and ventromedial cardiac nerves and, when present, the stellate cardiac nerve. Peak of the phasic diaphragm EMG and expiratory time were not significantly affected by stimulation of the VA. A significant decrease in inspiratory time was observed. Ipsilateral excitation and contralateral inhibition of the left and right triangularis sterni EMGs, respectively, were produced by stimulation of the VA. Stimulation of the other intrathoracic nerves produced a similar pattern of results. Conduction velocity determinations suggested that the afferents which produced the reflex responses are, at least in part, small A fibers.

Animals↗

PubMed1994

Interaction between chemoreceptor and stretch receptor inputs at medullary respiratory neurons.

The interaction between afferent inputs from carotid body chemoreceptors (CCRs) and from slowly adapting pulmonary stretch receptors (PSRs) on the discharge patterns of medullary inspiratory (I) and expiratory (E) neurons was characterized in thiopental sodium-anesthetized, paralyzed, ventilated dogs. A cycle-triggered ventilator was used to produce control and test pulmonary afferent input patterns. The CCRs were stimulated by phase-synchronized bolus injections of CO2-saturated saline into the common carotid arteries. Only those neurons whose discharge time course was altered by both inflation and CCR activation were studied. The dorsal respiratory group (DRG) I inflation-insensitive neurons were also included. Cycle-triggered histograms of unit activity were obtained for the neuronal responses to inflation, CO2 bolus, and their combination, as well as for the spontaneous control condition. Linearity of the interaction was tested by comparing the sum of the net individual responses to the net response of the combined afferent inputs. The results suggest that a linear (additive) interaction between CCR and PSR inputs exists for the DRG I inflation-sensitive neurons, the ventral respiratory group (VRG) I decrementing, and caudal VRG E augmenting neurons, while a nonadditive interaction exists for caudal VRG E decrementing bulbospinal neurons. The implications of these findings are discussed.

Afferent Pathways↗

PubMed1993

Selective contribution of two types of carotid sinus baroreceptors to the control of blood pressure.

This study was performed to determine if selective elimination of afferent input from two different types of previously described baroreceptors altered the ability of the dog to regulate blood pressure (BP), examining specifically if there was differential loss of baroreceptor control of tonic levels of baseline pressure versus dynamic changes in pressure. In the first series of experiments in this study, anodal block of the carotid sinus nerve was used to selectively block afferent input in a sequence from large-diameter A-fiber carotid baroreceptors (mostly type I) to smaller A-fiber and nonmyelinated C-fiber baroreceptors (mostly type II). In the second series of experiments, anesthetic block of the carotid sinus nerve with bupivacaine was used to selectively eliminate afferent input in reverse order from anodal block, first blocking input from baroreceptors with small afferent fibers and then additionally eliminating input from the larger-diameter A-fiber baroreceptors. The effects of selective elimination of each baroreceptor type were determined by monitoring baseline BP during constant carotid sinus pressure (CSP) perfusion of a vascularly isolated carotid sinus (tonic control) and obtaining baroreflex sensitivity (slope) during ramp pressure stimulations of the carotid sinus (dynamic control) under various blocking conditions. Low levels of anodal block significantly attenuated baroreflex sensitivity (-0.84 +/- 0.11 versus -0.63 +/- 0.10 mm Hg BP/mm Hg CSP) at levels of block that had no effect on tonic baseline BP (158.41 +/- 9.5 versus 160.7 +/- 9.5 mm Hg BP). In contrast, low levels of bupivacaine block produced significant increases in tonic BP (158.8 +/- 6.4 versus 169.0 +/- 6.5 mm Hg BP), whereas there was no effect on dynamic baroreflex sensitivity (-0.85 +/- 0.08 versus -0.73 +/- 0.08 mm Hg BP/mm Hg CSP). Thus, blocking large A-fiber baroreceptors resulted in significant decreases in baroreflex sensitivity without changes in baseline levels of BP, indicating primarily an attenuation in dynamic baroreflex regulation. Blocking of smaller A-fiber and unmyelinated C-fiber baroreceptors resulted in smaller decreases in baroreflex sensitivity and significant elevations in baseline BP, indicating a loss of tonic control of pressure. These results suggest that the two types of baroreceptors contribute differently to the regulation of blood pressure.

Afferent Pathways↗

PubMed1992

Differential control of sympathetic activity to kidney and skeletal muscle by ventral medullary neurons.

A rise in arterial blood pressure can be evoked by microinjections of D,L-homocysteic acid into localized regions of the ventrolateral medulla of the cat. Three patterns of sympathetic discharge can be identified during the pressor response. A differential pattern consisting of an increase in renal nerve activity and no change in sympathetic activity to skeletal muscle vasculature can be elicited from sites ventromedial to the caudal pole of the facial nucleus. From more lateral and caudal sites, a generalized sympatho-excitation is evoked in the outflow to both the kidney and hindlimb muscle vasculature. A third response consisting of a differential increase in muscle sympathetic activity simultaneous with a small decrease in renal nerve activity could be evoked from caudal sites, lateral to the inferior olives and superficial to the ventral surface. The results show that ventral medullary neurons can selectively activate sympathetic outflow to control specific vascular beds. These data may support the hypothesis that the ventrolateral medulla contains discrete groups of topographically arranged neurons that can differentially control sympathetic tone to various end-organs.

Animals↗

PubMed1992

Expiratory bulbospinal neurons of dogs. I. Control of discharge patterns by pulmonary stretch receptors.

To better understand expiratory bulbospinal (EBS) neuronal processing of afferent patterns from slowly adapting pulmonary stretch receptors (PSRs), the responses of these caudal medullary neurons to various inflation patterns were analyzed in thiopental sodium-anesthetized paralyzed dogs. Normocapnic ventilation was obtained from lung inflations delivered during the neural inspiratory phase of control respiratory cycles by a solenoid ventilator triggered by the onset of phrenic nerve activity. Test inflation patterns, delivered during the neural expiratory (E) phase of specific cycles, were separated by 6-10 control cycles and consisted of slow augmenting and decrementing ramps and steps. Transpulmonary pressure (Pt) was used as an index of PSR activity, and the discharge patterns of single EBS neurons were quantified using cycle-triggered histograms. Based on the time course of the discharge pattern during no-inflation cycles, two types of neurons were identified. Type D, the most common, exhibited a decrementing-like pattern, while type A exhibited an augmenting-plateau pattern. Plots of discharge frequency vs. Pt for type D neurons consisted of a linear excitatory phase (1 less than Pt less than 4.6 mmHg) and a linear inhibitory phase (4.6 less than Pt less than 12 mmHg). Type A neurons exhibited only a linear inhibitory phase for 3.3 less than Pt less than 12 mmHg. Because the responses to step inflations (4 s duration) exhibited only a small amount of time dependency, and the activation Pt of PSRs, but not of the other pulmonary receptors with vagal fibers, is in the proper range, it appears that PSRs may mediate both excitatory and inhibitory components of the neuronal response. These data suggest that discharge patterns of the caudal EBS neurons in dogs are highly dependent on the time course of Pt in a predictable manner, and implicate the importance of instantaneous lung volume in the control of the E musculature and the optimization of the breathing pattern.

Animals↗

PubMed1992

Expiratory bulbospinal neurons of dogs. II. Laterality of responses to spatial and temporal pulmonary vagal inputs.

Pulmonary mechanoreceptors with vagal fibers produce a combination of excitation and inhibition in the majority of the expiratory bulbospinal (EBS) neurons of dogs. Both aspects of this transpulmonary pressure-dependent neuronal response appear to be slowly adapting and activated at low pressure levels, suggesting the involvement of the slowly adapting pulmonary stretch receptors (PSRs). The purpose of the present study was to determine the contribution of different afferent pathways to each of the response components and to characterize the spatial and temporal processing of ipsi-, contra-, and bilateral vagal afferent inputs by two types of EBS neurons. For this purpose low-intensity electrical stimulation of the intact, desheathed, vagus nerves was used in thiopental sodium-anesthetized paralyzed dogs. The phrenic neurogram was used to synchronize both ventilation and stimulation. During test respiratory cycles, pulse trains (4-5 s duration) were applied during the neural expiratory phase to each and both vagus nerves. The mean discharge frequency (Fn) during the stimulus period was obtained from cycle-triggered histogram data. Plots of Fn vs. stimulus strength and Fn vs. stimulus frequency suggest that inhibition of both type D and type A EBS neurons is mediated mainly by the ipsilateral vagus nerve, and that the excitation of type D neurons is mediated bilaterally. These conclusions are also supported by inflation responses obtained before and after unilateral vagotomies. Differences in latencies and spatial and temporal summation characteristics suggest the possible involvement of different 1) types of PSRs, 2) central pathways, and/or 3) synaptic mechanisms in the biphasic response of the caudal ventral EBS neurons to lung inflation.

Afferent Pathways↗

PubMed1992

Acute resetting in two functionally different types of carotid baroreceptors.

The presence of two types of carotid sinus baroreceptors, as characterized by two different stimulus-response curves in an earlier study, suggests that each type may play a different role in the regulation of blood pressure. The discontinuous hyperbolic curve of the type I baroreceptors, marked by higher firing rates and greater sensitivity than the sigmoidal curve of type II baroreceptors, suggests that these baroreceptors would contribute more to the buffering of arterial pressure changes than the "tonically" active type II baroreceptors, which fired over greater pressure ranges and generally had spontaneous subthreshold discharge. The firing characteristics of type II baroreceptors suggest that these receptors would contribute more to regulation of tonic, baseline levels of arterial pressure. If this functional differentiation exists, the acute resetting characteristics of the two types of baroreceptors could be different. Resetting is defined as a shift in the response curve of a baroreceptor, marked by shifts in pressure threshold, in the same direction as the change in pressure to which it is exposed. Type I baroreceptors would be more likely to reset in response to a sustained acute change in pressure, since their primary role would be to prevent the initial change in pressure. However, type II baroreceptors would not reset to the acute change in pressure, since their primary role would be to maintain consistent information on the level of existing pressure. Therefore, this study was performed to examine the acute resetting ability of both types of baroreceptors by using a vascularly isolated carotid sinus preparation in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Respiratory responses to aortic and carotid chemoreceptor activation in the dog.

Respiratory responses arising from both chemical stimulation of vascularly isolated aortic body (AB) and carotid body (CB) chemoreceptors and electrical stimulation of aortic nerve (AN) and carotid sinus nerve (CSN) afferents were compared in the anesthetized dog. Respiratory reflexes were measured as changes in inspiratory duration (TI), expiratory duration (TE), and peak averaged phrenic nerve activity (PPNG). Tonic AN and AB stimulations shortened TI and TE with no change in PPNG, while tonic CSN and CB stimulations shortened TE, increased PPNG, and transiently lengthened TI. Phasic AB and AN stimulations throughout inspiration shortened TI with no changes in PPNG or the following TE; however, similar phasic stimulations of the CB and CSN increased both TI and PPNG and decreased the following TE. Phasic AN stimulation during expiration decreased TE and the following TI with no change in PPNG. Similar stimulations of the CB and CSN decreased TE; however, the following TI and PPNG were increased. These findings differ from those found in the cat and suggest that aortic chemoreceptors affect mainly phase timing, while carotid chemoreceptors affect both timing and respiratory drive.

Afferent Pathways↗

PubMed1991

Effects of epinephrine on firing characteristics of two functionally different types of carotid baroreceptors.

Sympathetic stimulation and catecholamine exposure have been shown to sensitize the arterial baroreceptors, but the extent or importance of this effect is not known. We performed this study to investigate the effects of sympathetic feedback on the carotid sinus baroreceptors, specifically examining the effect of the stimulation on the two different functional types of baroreceptors characterized in an earlier study. The existence of two baroreceptor function-response curves has suggested that the roles of the two functionally different baroreceptors may not be the same. If true, the effects of epinephrine exposure on baroreceptor firing characteristics may contribute to differential roles played by each baroreceptor type in the control of blood pressure. Single-fiber baroreceptor activity from a vascularly isolated carotid sinus was recorded during slow increases in carotid sinus pressure before and during exposure to epinephrine (10(-8) to 10(-6) M). Baroreceptor firing characteristics were determined from function curves plotting carotid sinus pressure versus nerve activity, with curve-fitting analysis of the hyperbolic type I and sigmoidal type II baroreceptor curves used to obtain threshold (Pth) and saturation (Psat) pressures, threshold (Fth) and saturation (Fsat) firing rates, and sensitivity (slope) for each baroreceptor before and during epinephrine exposure. The possible mechanisms of observed changes were examined using our previously published baroreceptor computer model. Epinephrine exposure was found to significantly increase sensitivity, Fth, and Fsat of both types of baroreceptors, with a relatively greater effect on type I sensitivity and on type II Fth and Fsat. Epinephrine also was found to increase the level of spontaneous discharge for type II baroreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Reflex ventilatory effects of KCl stimulation of lung receptors with sympathetic afferents.

The purpose of this study was to determine the reflex ventilatory effects produced by lung receptors with sympathetic afferent nerves. Seven dogs were anesthetized with sodium pentobarbital, placed on a ventilator, and vagotomized. The chest was opened through a mid-sternal incision. Diaphragm EMG (D-EMG), right and left triangularis sterni EMG (TS-EMG), systemic arterial blood pressure (BP), and tracheal pressure were recorded before and after the application of 2 M KCl to the right or left lung near the venous hilum. The reflex effects produced by KCl applied to the superior vena cava (SVC) and of mechanical distortion of the lungs were also studied. KCl applied to the right or left lung or right or left lung distortion produced significant increases in peak TS-EMG ipsilateral to the applied stimulus with no significant effects on the contralateral TS-EMG. BP, inspiratory time, expiratory time, or peak D-EMG were not significantly affected, except for a decrease in inspiratory time when KCl was applied to the left lung and a decrease in BP with distortion of the left lung. KCl applied to the SVC produced a significant reflex increase in the right TS-EMG. The primary reflex response to chemical stimulation of lung receptors with sympathetic afferents was an increase in expiratory muscle activity. Additionally, mechanical stimulation may also activate these receptors. Furthermore, receptors which produce similar reflex responses are located on the SVC. That the reflex responses produced by intrathoracic receptors with sympathetic afferents were unilateral suggests that spinal mechanisms are involved.

Animals↗

PubMed1990

Firing characteristics of single-fiber carotid sinus baroreceptors.

This study examined firing patterns of single-fiber carotid baroreceptors in response to slow ramp increases in carotid sinus pressure (1-2 mm Hg/sec) in vascularly isolated carotid sinus preparations in thiopental-anesthetized dogs (25 mg/kg, plus 10 mg/kg/hr). Two general types of baroreceptor discharge patterns were obtained: 1) type I, a discontinuous, hyperbolic pattern characterized by a sudden onset of discharge at threshold pressure with a relatively high threshold frequency, which gradually increased to a higher saturation firing rate and 2) type II, a continuous, sigmoidal pattern characterized by a gradual increase in discharge above threshold pressure and a relatively low threshold frequency and saturation firing rate. Type II baroreceptor curves typically showed spontaneous discharge below threshold pressure and significantly lower sensitivities, threshold frequency, saturation firing rate, and threshold pressure than those of type I receptors. However, the saturation pressures and operating ranges of the type II receptors were greater than those of type I receptors, and the pressure at which type II receptors had their greatest sensitivity was greater than that for type I receptors. Type I baroreceptors generally had large myelinated afferent A fibers; type II baroreceptors generally had smaller A and unmyelinated C fibers, based on conduction velocities. The presence of spontaneous activity with type II baroreceptors, combined with significantly lower sensitivities and wider pressure operating ranges seen relative to type I baroreceptors, suggests that these receptors may primarily serve to provide information on tonic, or baseline, levels of arterial blood pressure to the central cardiovascular centers. The sudden onset of discharge, higher sensitivities, and narrower operating ranges of type I baroreceptors suggest that their primary role may be to provide information on dynamic, sudden changes in arterial pressure.

Afferent Pathways↗

PubMed1990

Experimental and modeling study of the excitability of carotid sinus baroreceptors.

In this study we examined the effects of blockade of a transient K+ current with 4-aminopyridine (4-AP) on the static stimulus-response relation of myelinated carotid sinus baroreceptors (n = 8), using a vascularly isolated sinus preparation in sodium thiopental-anesthetized dogs. In one class of baroreceptors (type I), which did not fire spontaneously below the pressure threshold (Pth), 4-AP (10(-5) to 10(-4) M) decreased Pth in a dose-dependent manner and transformed the stimulus-response relation from a discontinuous, hyperbolic shape to a sigmoidal, continuous curve. After exposure to 10(-4) M of 4-AP, baroreceptors were spontaneously active below Pth. These effects of 4-AP were more pronounced in baroreceptors with a high control Pth and were independent of enhanced neurotransmitter release or changes in carotid sinus distensibility. In contrast, 4-AP had relatively little effect on type II baroreceptors, which under control conditions are characterized by a continuous, sigmoidal stimulus-response curve. We believe that these effects of 4-AP on baroreceptor discharge were mediated by blockade of a transient K+ conductance that was present at the receptor spike-initiation zone. This hypothesis was examined using a mathematical model based on the Hodgkin-Huxley axon, but modified to include the transient K+ conductance. The modeling results showed that the minimum current necessary to elicit action potential firing is an extremely sensitive function of the magnitude of this K+ conductance, supporting our experimental results obtained with 4-AP. Our findings suggest that a transient K+ conductance might play a role in the determination of Pth and that differences between type I and II receptors could be the result of differences in the effectiveness of this conductance in controlling spike-initiation zone excitability.

4-Aminopyridine↗

PubMed1989

Processing of pulmonary afferent input patterns by respiratory I-beta neurons.

To characterize the dynamics of the control of respiratory I-beta neurons by slowly adapting pulmonary stretch receptors, the neuronal discharge responses to lung inflation and electrically induced vagal input patterns were analyzed. Unitary recordings from single medullary I-beta neurons and whole phrenic nerve activity were recorded in chloralose-urethan-anesthetized paralyzed cats. Neuronal discharge patterns were quantified in terms of cycle-triggered histograms. The net response to a test afferent input pattern generated during neural inspiration was expressed as the difference between the central component of I-beta activity and the total response. The central component was obtained during control respiratory cycles in which lung inflation occurred during neural expiration and no vagal feedback occurred during neural inspiration. For a set of test inflations with different ramp rates, the net responses, measured at fixed times with respect to the onset of neural inspiration, were linearly related to transpulmonary pressure. However, the slopes of these relationships increased as a function of time during neural inspiration. Neuronal responses to electrically induced ramp vagal input patterns were similar to those produced by ramp inflation. The net response due to electrically induced ipsilateral step patterns consisted of a rapid excitatory and a slow inhibitory component, whereas only the slow inhibitory component was observed for contralateral patterns. The implications of these findings with respect to the modes of neural processing and effects on phrenic output patterns are discussed.

Afferent Pathways↗