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R C Foehring

Publications and source records attributed to R C Foehring.

At least 37 records · Page 2Linked to original sources
PubMed1996

Isolation and characterization of a persistent potassium current in neostriatal neurons.

1. Depolarization-activated, calcium-independent potassium (K+) currents were studied with the use of whole cell voltage-clamp recording from neostriatal neurons acutely isolated from adult (> or = 4 wk old) rats. The whole cell K+ current was composed of transient and persistent components. The aims of the experiments were to isolate the persistent component and then to characterize its voltage dependence and kinetics. 2. Application of 10 mM 4-aminopyridine (4-AP) completely blocked the transient currents while reducing the persistent current by approximately 40% [50% inhibitory concentration (IC50), of blockable current = 125 microM]. The persistent K+ current also was reduced by tetraethylammonium (TEA). Two components to the TEA block were present, having IC50s of 125 microM (23% of the blockable current) and 5.9 mM (77% of the blockable current). Collectively, these results suggested that the persistent components of the total K+ current was pharmacologically heterogeneous. The properties of the 4-AP-resistant, persistent K+ current (IKrp) were subsequently studied. 3. The kinetics of activation and deactivation of IKrp were voltage dependent. Examination of the entire activation/deactivation time constant profile showed that it was bell shaped, with time constants being moderately rapid (tau approximately 50 ms) at membrane potentials corresponding to the resting potential of neostriatal cells (approximately -80 mV), becoming considerably longer (tau approximately 100 ms) at potentials near the cells' spike thresholds (approximately -45 mV), and decreasing to a minimum (tau approximately 5 ms) at potentials associated with the peak of the cells' action potentials (approximately +20 mV). The inactivation kinetics of IKrp also were voltage dependent. The time constants of inactivation varied between 1 and 8 s at potentials between -10 and +35 mV. 4. Unlike persistent K+ currents in many other cell types, IKrp activated at relatively hyperpolarized membrane potentials (approximately -70 mV). The Boltzmann function describing activation had a half-activation voltage of -13 mV and a slope factor of 12 mV. In addition, the Boltzmann function describing the voltage dependence of inactivation of IKrp had a relatively depolarized half-inactivation voltage of -55 and a large slope factor of 19 mV, indicating that this current was available over a broad range of membrane potentials (between -100 and -10 mV). 5. Neostriatal neurons recorded in vivo exhibit subthreshold shifts in membrane potential of variable duration (tens of ms to s) from a hyperpolarized resting state to a depolarized state that is limited in amplitude just below spike threshold. The voltage dependence of activation and inactivation of IKrp indicates that it will be available on depolarization from the hyperpolarized state. However, the slow activation rate of this current suggests that it will contribute little either to limiting the amplitude of the initial depolarization associated with entry into the depolarized state or to depolarizing episodes of short duration (e.g., < 50 ms). However, IKrp should limit the amplitude of membrane depolarizations associated with prolonged excursions into the depolarized state.

4-Aminopyridine↗
PubMed1996

Pharmacological dissection of high-voltage-activated Ca2+ current types in acutely dissociated rat supraoptic magnocellular neurons.

1. We used pharmacological blockers and whole cell voltage-clamp recordings from acutely dissociated magnocellular neurons from the rat supraoptic nucleus to test for the presence of L-, N-, P-, Q-, and R-type calcium currents. 2. We found clear evidence for L-type (dihydropyridine sensitive), N-type (blocked by omega-conotoxin (GVIA), and P-type (blocked by omega-agatoxin IVA) currents. Nifedipine blocked 28 +/- 2% (mean +/- SE) of the current, omega-conotoxin GVIA blocked 26 +/- 4%, and omega-agatoxin IVA (25-30 nM) blocked 17 +/- 4%. In addition, omega-conotoxin MVIIC blocked about half (54 +/- 2%) of the current remaining after L-, N-, and P-type currents were blocked, suggesting the presence of Q-type currents. 3. About 20% of the whole cell current was unblocked by the combination of all four blockers, suggesting the presence of a fifth current type. This residual current inactivated slowly at -10 mV.

Animals↗
PubMed1995

Alterations in intracellular calcium chelation reproduce developmental differences in repetitive firing and afterhyperpolarizations in rat neocortical neurons.

Many 1-week-old rat sensorimotor cortical neurons exhibit extreme spike-frequency adaptation (neurons only fire for the first 100-250 ms of a 1 s current injection) accompanied by a large, prolonged afterhyperpolarization (AHP). Relatively greater expression of a Ca-dependent K+ current appears to underlie the extreme adaptation observed in immature cells. In the present study, we examined whether altering intracellular Ca2+ buffering by introducing Ca2+ chelators via the recording electrode could reproduce the age-related differences in firing and AHPs. We studied firing behavior and AHPs in 1-week-old and adult neocortical neurons with sharp microelectrodes, under three recording conditions: no chelator, 2 mM BAPTA, or 100-200 mM BAPTA. Our principal findings in regard to firing behavior and AHPs were that (1) adult-low BAPTA neurons mimicked 1 week-control cells, (2) 1 week-high BAPTA neurons were similar to adult-control cells, (3) a greater percentage of 1 week-low BAPTA neurons showed complete adaptation, and (4) adult neurons impaled with high BAPTA electrodes fired in a burst-spiking mode. These data suggest that Ca2+ regulation is qualitatively different in immature and adult neurons.

Action Potentials↗
PubMed1995

Characterization of pharmacologically identified voltage-gated calcium channel currents in acutely isolated rat neocortical neurons. I. Adult neurons.

1. Whole cell recordings were obtained from pyramidal neurons acutely dissociated from the sensorimotor cortex of adult rats. 2. Whole cell calcium channel currents were similar in appearance when elicited from holding potentials of -90 or -40 mV. With 5 mM Ba2+ as the charge carrier, currents began to activate at approximately -45 mV, peaked at approximately -10 mV, and had an apparent reversal potential of approximately +45 mV. Current amplitude and voltage dependence varied with the concentration and identity of the charge carrier (Ca2+ vs. Ba2+). Calcium channel currents were blocked completely by > 200 microM Cd2+ (IC50 approximately 3.5 microM). 3. We determined saturating doses for blockade of currents by nifedipine (Nif), omega-conotoxin GVIA (CgTx), and omega-agatoxin IVA (AgTx) in adult cells. We also tested the selectivity of these compounds by applying them in combination and in different orders. We found the three compounds to be highly, but not perfectly, specific. 4. L-type current was operationally defined as that blocked by 5 microM Nif, N-type current as that blocked by 1 microM CgTx, and P-type current as that blocked by 100 nM AgTx. In adult cells, each of these compounds blocked 30-35% of the current. When all three blockers were applied concurrently, approximately 80% of the current was blocked (20% of current was resistant to the 3 blockers). 5. Few biophysical differences were found between the pharmacologically defined current components in adult cells. The resistant current had a more rapid time-to-peak, inactivated more rapidly and completely, and activated at more negative potentials than the other three types.

Animals↗
PubMed1995

Characterization of pharmacologically identified voltage-gated calcium channel currents in acutely isolated rat neocortical neurons. II. Postnatal development.

1. Whole cell recordings were obtained from pyramidal neurons acutely dissociated from the sensorimotor cortex of adult (from Lorenzon and Foehring, companion paper) and immature rats postnatal day 1 (P1) to adult. 2. Whole cell calcium channel currents were similar in appearance at all ages. Current amplitudes and estimated densities were initially low (approximately 16 pA/pF at ages < P6) and increased gradually, attaining adult values at approximately 4-5 wk postnatally (approximately 100 pA/pF). 3. L-type current was operationally defined as that blocked by 5 microM nifedipine, N-type current as that blocked by 1 microM omega-conotoxin GVIA, and P-type current as that blocked by 100 nM omega-agatoxin IVA. A resistant current remained in the presence of the combination of these three blockers. The proportions of these four current types did not change during ontogeny. 4. Few biophysical differences were found between the pharmacologically defined current components in adult or 1-wk-old cells. At both ages the resistant current had a more rapid time-to-peak and inactivated more completely and rapidly than the other three types. Resistant currents also activated at more negative potentials. N-, L-, and P-type currents activated at more positive potentials in 1-wk-old cells than in adult cells. For the resistant current, the voltage dependence of activation was not significantly different between the two ages.

Aging↗
PubMed1993

The ontogeny of repetitive firing and its modulation by norepinephrine in rat neocortical neurons.

The postnatal ontogeny of electrical properties was studied in rat sensorimotor cortical neurons (P6 to adult) using intracellular recording in an in vitro slice preparation. Many action potential properties and input resistance changed during the first 4 postnatal weeks. Repetitive firing behavior also changed during the first postnatal month. Spike-frequency adaptation was much stronger in immature neurons. At 1 week postnatal, the majority of cortical neurons would only fire for less than 200 ms regardless of the intensity of long depolarizing current injections. These cells were normal in other parameters and could fire throughout a depolarizing current injection in the presence of inorganic calcium channel blockers or norepinephrine (NE), suggesting that the inability to fire was not due to injury. The frequency with which we encountered cells with this extreme adaptation decreased with age. Spike-frequency adaptation in immature neurons appears to be primarily controlled by Ca-dependent K+ conductances as in mature neurons. In mature and immature neurons, three afterhyperpolarizations (AHPs) could be distinguished by their rate of decline. The fast AHP followed repolarization of a single spike and was only partially Ca- and K-dependent. The medium duration AHP was Ca-dependent and apamin-sensitive and the slow AHP was partially Ca-dependent and not blocked by apamin. NE decreased the slow Ca-dependent AHP via beta-adrenergic receptors. This effect of NE on AHPs appeared qualitatively similar throughout postnatal development. NE had a proportionately greater effect in younger neurons, however, due to their relatively larger slow AHP. The quantitative differences of NE's action on the slow AHP (sAHP) led to a qualitative difference in NE's effect on firing behavior. The effects of NE on firing behavior may therefore be greater during times critical for cortical maturation.

Action Potentials↗
PubMed1993

Voltage-gated potassium currents in acutely dissociated rat cortical neurons.

1. We describe three outward K+ current components in acutely dissociated neurons from rat sensorimotor cortex on the basis of inactivation kinetics and voltage dependence. 2. The fast A current (IAf) was completely inactivated at -40 mV and half-inactivated at -52 mV. It activated [time to peak (TTP) 8 ms at -10 mV] and was inactivated (tau inact = 12 ms at -10 mV) rapidly. Recovery from inactivation had a time constant of approximately 80 ms at -100 mV. It was insensitive to tetraethyl ammonium (TEA) and dendrotoxin but was blocked by 4-aminopyridine (4-AP, IC50 = 1 mM). 3. The slowly inactivating current (IKS) was the largest current seen in acutely dissociated adult neurons. It was completely inactivated at -40 mV, half-inactivated at -98 mV, and was kinetically slower (TTP = 130 ms at -10 mV; tau inact = 293 ms at -10 mV) than the fast A current. Deactivation tails were fit with the sum of two exponentials with time constants of 2-10 and 15-40 ms. IKS recovered from inactivation with a time constant of approximately 1,200 ms at -100 mV. 4. There were two components that inactivated with even slower kinetics. The very slowly inactivating current (IKSS) was operationally defined as the current remaining after a 5-s hold at -40 mV. One component inactivated with a time constant of 1,927 ms at -10 mV. The other component showed no inactivation over a 5-s test command, but in 40- to 50-s steps to -10 mV, inactivated with a tau of approximately 20 s. The very slowly inactivating current activated with similar kinetics to IKS (TTP = 121 ms at -10 mV), and two deactivation tails, with kinetics similar to those after the -100 mV prepulse, were observed after holding at -40 mV. 5. Both IKS and IKSS were sensitive to TEA. Seventy-six percent (76%) of IKSS was blocked by 30 mM TEA. Two components to the TEA block were present for IKSS, with IC50s of 88 microM (67% of blockable current) and 7 mM (33%). Seventy percent (70%) of IKS was blocked by 30 mM TEA. For the IKS current, there were also two effective concentrations, with IC50s of 8 microM (21% of blockade current) and 3 mM (79%). 6. IKS and IKSS were also sensitive to 4-AP. Seventy-six percent (76%) of IKSS was blocked by 3-5 mM 4-AP. IKSS exhibited two components of 4-AP block.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1992

Relationship between repetitive firing and afterhyperpolarizations in human neocortical neurons.

1. Human neocortical neurons fire repetitively in response to long depolarizing current injections. The slope of the relationship between average firing frequency and injected current (f-I slope) was linear or bilinear in these cells. The mean steady-state f-I slope (average of the last 500 ms of a 1-s firing episode) was 57.8 Hz/nA. The instantaneous firing rate decreased with time during a 1-s constant-current injection (spike frequency adaptation). Also, human neurons exhibited habituation in response to a 1-s current stimulus repeated every 2 s. 2. Afterhyperpolarizations (AHPs) reflect the active ionic conductances after action potentials. We studied AHPs with the use of intracellular recordings and pharmacological manipulations in the in vitro slice preparation to 1) gain insight into the ionic mechanisms underlying the AHPs and 2) elucidate the role that the underlying currents play in the functional behavior of human cortical neurons. 3. We have classified three AHPs in human neocortical neurons on the basis of their time courses: fast, medium, and slow. The amplitude of the AHPs was dependent on stimulus intensity and duration, number and frequency of spikes, and membrane potential. 4. The fast AHP had a reversal potential of -65 mV and was eliminated in extracellular Co2+, tetraethylammonium (TEA) or 4-aminopyridine, and intracellular TEA or CsCl. These manipulations also caused an increase in spike width. 5. The medium AHP had a reversal potential of -90 to -93 mV (22-24 mV hyperpolarized from mean resting potential). This AHP was reduced by Co2+, apamin, tubocurare, muscarine, norepinephrine (NE), and serotonin (5-HT). Pharmacological manipulations suggest that the medium AHP is produced in part by 1) a Ca-dependent K+ current and 2) a time-dependent anomalous rectifier (IH). 6. The slow AHP reversed at -83 to -87 mV (14-18 mV hyperpolarized from mean resting potential). This AHP was diminished by Co2+, muscarine, NE, and 5-HT. The pharmacology of the slow AHP suggests that a Ca-dependent K+ current with slow kinetics contributes to this AHP. 7. The currents involved in the fast AHP are important in spike repolarization, control of interspike interval during repetitive firing, and prevention of burst firing. Currents underlying the medium and slow AHPs influence the interspike interval during repetitive firing and produce spike frequency adaptation and habituation.

4-Aminopyridine↗
PubMed1991

Contributions of low-threshold calcium current and anomalous rectifier (Ih) to slow depolarizations underlying burst firing in human neocortical neurons in vitro.

The slow depolarization that underlies the voltage-dependent burst-firing behavior of human neocortical neurons is mediated by a low-threshold calcium conductance in concert with the anomalous rectifier current, Ih. The slow depolarization could be elicited by depolarization from negative membrane potentials or as a rebound following hyperpolarization. The rebound depolarization was time- and voltage-dependent. Most of the slow depolarization was blocked by inorganic calcium blockers. The remainder of the depolarization and the 'sag' in the hyperpolarizing voltage responses were blocked by extracellular Cs+.

Action Potentials↗
PubMed1991

Developmental regulation of a slowly-inactivating potassium conductance in rat neostriatal neurons.

In late embryonic and early post-natal rat neostriatal neurons, the voltage-dependent potassium currents activated by depolarization are largely attributable to a rapidly inactivating A-current and a delayed rectifier current. Over the first 4 weeks of post-natal life, a third potassium current emerges in most cells. This slowly inactivating conductance is distinct from the A-current and delayed rectifier in voltage-dependence, kinetics and pharmacology. The properties of this conductance suggest that it may be of central importance to the integrative behavior of neostriatal neurons by controlling such features as first spike latency and interspike interval.

Animals↗
PubMed1991

Correlation of physiologically and morphologically identified neuronal types in human association cortex in vitro.

1. We examined whether the three physiologically defined neuron types described for rodent neocortex were also evident in human association cortex studied in an in vitro brain slice preparation. We also examined the relationship between physiological and morphological cell type in human neocortical neurons. In particular, we tested whether burst-firing neurons were numerous in regions of human cortex that are susceptible to seizures. 2. Although we sampled regular-spiking and fast-spiking neurons, we observed no true burst-firing neurons, as defined for rodent cortex. We did find neurons that displayed a voltage-dependent shift in firing behavior. Because this behavior was due, in large part, to a low-threshold calcium conductance, we called these cells low-threshold spike (LTS) neurons. 3. Regular-spiking neurons and LTS neurons only differed in the voltage dependence of firing behavior and the first few interspike intervals (ISIs) of repetitive firing in response to small current injections (from hyperpolarized membrane potentials). Because of the general similarities between the two types, we consider the LTS cells to be a subgroup of regular-spiking cells. 4. All biocytin-filled regular-spiking neurons were spiny and pyramidal and found in layers II-VI. The lone filled fast-spiking cell was aspiny and nonpyramidal (layer V). The LTS neurons were morphologically heterogeneous. We found 80% of LTS neurons to be spiny and pyramidal, but 20% were aspiny nonpyramidal cells. LTS neurons were located in layers II-VI. 5. In conclusion, human association cortex contains two of three physiological cell types described in rodent cortex: regular spiking and fast spiking. These physiological types corresponded to spiny, pyramidal, and aspiny, nonpyramidal cells, respectively. We sampled no intrinsic burst-firing neurons in human association cortex. LTS neurons exhibited voltage-dependent changes in firing behavior and were morphologically heterogeneous: most LTS cells were spiny and pyramidal, but two cells were found to be aspiny and nonpyramidal. It is not clear whether the absence of burst-firing neurons or the morphological heterogeneity of LTS neurons are due to species differences or differences in cortical areas.

Association Learning↗
PubMed1990

Two patterns of firing in human neocortical neurons.

Intracellular recordings were made in slices of human neocortex removed for surgical treatment of epilepsy. In response to prolonged suprathreshold current injection, regular spiking neurons (67.5% of sample) responded by repetitive firing throughout the stimulus from all membrane potentials. Bursting neurons (32.5% of sample) responded with a burst of 2-3 spikes which rode upon a voltage-dependent slow depolarization. Bursting behavior was only observed from membrane potentials more negative than -65 mV.

Cerebral Cortex↗
PubMed1990

Motoneuron and muscle-unit properties after long-term direct innervation of soleus muscle by medial gastrocnemius nerve in cat.

1. This study addresses the following questions. 1) In a previous experiment, when the combined lateral gastrocnemius-soleus nerve was cross-innervated by the medial gastrocnemius (MG) nerve, was the predominance of slow muscle units in soleus muscle a result of selective routing of slow motor axons into soleus? 2) Is MG-nerve-induced conversion of soleus muscle fibers from slow to fast more complete at very long (18 mo vs. 9-11 mo) postoperative times? 3) Do MG motoneurons that cross-innervate soleus muscle recover their normal membrane electrical properties at very long postoperative times? 2. The proximal portion of approximately one-third of the MG nerve was coapted directly with the distally isolated soleus nerve. The MG muscle remained innervated by the unoperated portion of the MG nerve. At 6, 10, or 18 mos postoperative, motoneuron and/or muscle-unit properties were determined for MG motoneurons innervating MG, soleus, or neither muscle, and for axotomized soleus motoneurons. 3. In the partially denervated MG muscle, the proportions of motor units of each type were normal. This suggests that the population of MG motor axons that had been directed to the soleus nerve also contained a representative distribution of MG motoneuron types. 4. Most motor units (74%) in cross-innervated soleus (Xsoleus) were type S (based on muscle-unit contractile properties), in spite of the soleus nerve's having been cross-connected by approximately 75% fast MG motoneurons. Thus, even at very long postoperative times, slow soleus muscle units resisted conversion by fast MG motoneurons. 5. Thirty-two percent of MG motoneurons that had been cross-connected to soleus nerve elicited no measurable muscle contraction, compared with approximately 10% in previous reinnervation experiments in which the MG nerve was coapted with the MG or lateral gastrocnemius-soleus nerve. Thus MG motoneurons may be disadvantaged in their ability to innervate soleus muscle fibers. 6. It appears that at long postoperative times, those fast MG motoneurons tha had innervated large soleus muscle units had failed to convert those muscle fibers to fast types and had failed also to recover their normal motoneuron electrical properties. Conversion and recovery did occur for fast MG motoneurons that innervated small soleus muscle units and for slow MG motoneurons.

Animals↗
PubMed1989

Norepinephrine selectively reduces slow Ca2+- and Na+-mediated K+ currents in cat neocortical neurons.

1. The effects of norepinephrine (NE) and related agonists and antagonists were examined on large neurons from layer V of cat sensorimotor cortex ("Betz cells") were examined in a brain slice preparation using intracellular recording, constant current stimulation and single microelectrode voltage clamp. 2. Application of NE (0.1-100 microM) usually caused a small depolarization from resting potential; hyperpolarizations were rare. Application of NE reversibly reduced rheobase and both the Ca2+- and Na+-dependent portions of the slow afterhyperpolarization (sAHP) that followed sustained firing evoked by constant current injection. The faster Ca2+-dependent medium afterhyperpolarization (mAHP), the fast afterhyperpolarization (fAHP), the action potential, and input resistance were unaffected. 3. The changes in excitability produced by NE application were most apparent during prolonged stimulation. The cells exhibited steady repetitive firing to currents that were formerly ineffective. The slow phase of spike frequency adaptation was reduced selectively and less habituation occurred during repeated long-lasting stimuli. The relation between firing rate and injected current became steeper if firing rate was averaged over several hundred milliseconds. 4. During voltage clamp in TTX, NE application selectively reduced the slow component of Ca2+-mediated K+ current. The faster Ca2+-mediated K+ current was unaffected, as were two voltage-dependent, transient K+ currents, the anomalous rectifier and leakage conductance measured at resting potential. Depolarizing voltage steps in the presence of Cd2+ revealed an apparent time- and voltage-dependent increase of the persistent Na+ current after NE application. The voltage-clamp results suggested ionic mechanisms for all effects seen during constant current stimulation except the depolarization from resting potential. The latter was insensitive to Cd2+ and TTX and occurred without a detectable change in membrane conductance. 5. NE application did not alter Ca2+ spikes evoked in the presence of TTX and 10 mM TEA. Inward Ca2+ currents examined during voltage clamp in TTX (with K+ currents reduced) became slightly larger after NE application. We conclude that NEs reduction of the slow Ca2+-mediated K+ current is not caused by reduction of Ca2+ influx. 6. Effects on membrane potential, rheobase, and the sAHP were mimicked by the beta-adrenergic agonist isoproterenol, but not by the alpha-adrenergic agonists clonidine or phenylephrine at higher concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Histochemistry of flight muscles in the Jamaican fruit bat, Artibeus jamaicensis: implications for motor control.

Two fast-twitch fiber types are histochemically identified in the primary flight muscles of Artibeus jamaicensis. These are classified as type IIa and IIb according to an acid-preincubation staining protocol for myosin ATPase. All fibers in the bat flight muscles exhibit relatively intense staining properties for NADH-TR, suggesting a high oxidative capacity. The glycolytic potential of all fibers is rather low, as assessed by stains for alpha-GPD. This two-type histochemical profile appears to parallel biphasic electromyographic patterns observed in these muscles and leads us to propose that flight muscle histochemistry and activation are mediated by a "two-gear" neuromuscular control system. In contrast, earlier studies on Tadarida brasiliensis demonstrate the existence of a "one-gear" neuromuscular control system, exemplified by the presence of one fiber type. These observations are discussed with respect to the natural history and flight styles of several species.

Adenosine Triphosphatases↗
PubMed1988

Relation of whole muscle contractile properties to source of innervation.

This work investigated the extent to which constituent proportions of fast- and slow-twitch muscle units determine whole muscle contractile properties. We employed several self- and cross-reinnervation models using synergistic homogeneous and heterogeneous muscles. By comparing the present data with previously published single-unit studies on the same animals, we confirmed that the whole muscle data provide a weighted ensemble of single-unit effects. They corroborate conclusions based upon single-unit data concerning the proportions of fast- and slow-twitch units, the degree of recovery, and the alteration of force- and speed-related properties of muscle by nerve. In particular, the shape of the whole muscle isometric twitch was a reliable indicator of the relative proportions of fast- and slow-twitch motor units in the muscle. The half-rise time was an indicator of the presence or absence of fast units, and the half-relaxation time was an indicator of the presence of slow units.

Animals↗
PubMed1988

Multiple potassium conductances and their functions in neurons from cat sensorimotor cortex in vitro.

1. Potassium conductances were studied in large layer V neurons using an in vitro slice preparation of cat sensorimotor cortex. The kinetics and pharmacological sensitivity of K+ currents were studied directly using single microelectrode voltage clamp and indirectly by evoking single or multiple spikes and recording the spike repolarization and subsequent afterhyperpolarizations (AHPs). 2. A fast-decaying afterhyperpolarization (fAHP) and a subsequent medium-duration afterhyperpolarization (mAHP) followed a single spike. The amplitude and duration of the mAHP increased when multiple spikes were evoked at a fast rate (e.g., 100 Hz), and a slower afterhyperpolarization (sAHP) appeared only after sustained repetitive firing. 3. All AHPs were reduced by membrane potential hyperpolarization and raised extracellular K+ concentration, suggesting they were caused by an increased K+ conductance. Only the mAHP and sAHP reversed at the estimated value of potassium equilibrium potential (-100 mV), whereas the mean reversal potential of the fAHP was nearly identical to the mean value of resting potential (-71 mV). 4. Mechanisms underlying spike repolarization, the fAHP, and the mAHP were investigated. Two rapidly activating outward currents, a fast-inactivating current and a slowly inactivating delayed rectifier, were detected by voltage clamp. Both currents were reduced rapidly by tetraethylammonium (TEA). The fast transient current was reduced slowly after divalent cations were substituted for Ca2+ (through a mechanism unrelated to blockade of Ca2+ channels), whereas the delayed rectifier was unaffected. 5. Spike duration was increased and the fAHP was abolished only by blocking agents that reduced the fast outward currents. Effects of extracellular and intracellular TEA were similar. Effects of TEA and Ca2+-free perfusate were additive and resembled the effects of intracellular Cs+. The addition of apamin, d-tubocurare, or Cd2+ was ineffective. We conclude that the two fast outward currents reflect pharmacologically and kinetically separate K+ conductances that are primarily responsible for spike repolarization and the fAHP. 6. Voltage-clamp studies revealed two additional outward currents, which were persistent and Ca2+-mediated. Each current activated and deactivated slowly, but the kinetics of one component were approximately 10 times slower than the other. The decay of these currents gave rise to AHPs resembling the mAHP and the early sAHP. 7. Neither the mAHP nor the sAHP was reduced by TEA. The mAHP was reduced when divalent cations were substituted for Ca2+ or when Cd2+, apamin, or d-tubocurare were added.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗