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J J Kendig

Publications and source records attributed to J J Kendig.

At least 55 records · Page 3Linked to original sources
PubMed1989

Enflurane-induced burst discharge of hippocampal CA1 neurones is blocked by the NMDA receptor antagonist APV.

The basis for the hyperexcitability and seizure activity associated with enflurane anaesthesia was investigated using extracellular and intracellular recording in rat hippocampal brain slices. Enflurane produced seizure-like burst discharges in CA1 pyramidal neurones, accompanied by depressed field potential amplitudes and a reduced threshold for synaptically evoked population spikes. However, threshold for action potentials evoked by intracellular current injection did not change, nor did action potential amplitude, duration or spike frequency accommodation in single neurones. Enflurane 2.0 vol% hyperpolarized CA1 neurones (3.1 (SD 1.3)mV), decreased membrane conductance (12 (6)% below control), and depressed EPSP amplitudes (34% of control) (P less than 0.01). Enflurane appeared to enhance both intrinsic and synaptically mediated inhibitory potentials. The N-methyl-D-aspartate (NMDA) receptor antagonist amino-phosphonovalerate (APV) 5-20 mumol litre-1 completely blocked seizure-like burst discharge of CA1 neurones in the presence of enflurane, and the enflurane-induced reduction of population spike threshold; it did not alter anaesthetic depression of EPSP amplitude. Thus enflurane-induced burst discharge of CA1 neurones appeared to involve an enhancement of excitatory synaptic transmission rather than depression of intrinsic or synaptic inhibition.

2-Amino-5-phosphonovalerate↗
PubMed1988

Bupivacaine is an effective potassium channel blocker in heart.

The local anesthetic agent bupivacaine increases action potential duration in isolated frog atrial myocytes, and blocks two potassium conductances, IK and IK1. The effective concentrations, particularly for IK, are similar to those which depress the sodium conductance. Potassium channel block may thus contribute to bupivacaine's reported cardiotoxicity.

Action Potentials↗
PubMed1988

Pressure reversal of anaesthesia: a synaptic mechanism.

Hyperbaric pressure induces seizures and increases anaesthetic requirements ("pressure reversal of anaesthesia"), but both pressure and anaesthetic agents depress excitatory synaptic transmission. The present study has attempted to resolve this paradox. The interaction between helium pressure to 10.1 MPa and anaesthetic agents (pentobarbitone, halothane, methoxyflurane) was investigated at a crustacean glutaminergic excitatory neuromuscular junction which can be modulated by GABA inhibition. Both pressure and the anaesthetics depressed the singly evoked excitatory junctional potential (EJP). During repetitive stimulation, both pressure and pentobarbitone antagonized their own depressant effects by enhancing tetanic potentiation. The additive enhancement at 10.1 MPa was sufficient to increase the pentobarbitone-depressed response above the corresponding normobaric level. No significant antagonism between pressure and any of the anaesthetics was observed on the properties of EJP amplitude and time course, facilitation, potentiation or inhibition. Additivity rather than antagonism is the basis for pressure reversal of anaesthetic depression at this model synapse. The functional antagonism is therefore indirect, and probably involves multiple sites of action for both pressure and anaesthetics.

Action Potentials↗
PubMed1988

Synaptic integrative properties at hyperbaric pressure.

1. Because hyperbaric pressure profoundly depresses excitatory synaptic transmission, it has proved difficult to account for its excitatory effects in the CNS. We tested the hypothesis that hyperbaric pressure might increase excitation by enhancing facilitation and potentiation during repetitive synaptic activation, and/or by selectively depressing inhibitory synaptic transmission. Intracellular microelectrode recordings were obtained from crustacean muscle fibers innervated by single identifiable excitor and inhibitor motor neurons; the preparations were exposed to pressures of 0.1-10.1 MPa. 2. Hyperbaric pressure reduced the amplitude of the singly evoked excitatory junctional potential (EJP), enhanced paired-pulse facilitation, and increased the potentiation elicited by trains of stimuli. The potentiated EJP at 10.1 MPa approached the comparable response evoked at normobaric pressure. 3. Hyperbaric pressure also depressed inhibitory synaptic transmission, measured as depression of the EJP by the inhibitor motor neuron. However, pressure depressed excitatory and inhibitory synaptic transmission to the same extent. Thus there appears to be no selective effect of pressure on the GABA-activated chloride channel. The amplitude of the inhibited EJP at 10.1 MPa remained below that at normobaric pressure, even during repetitive stimulation. 4. The results do not support the hypothesis that pressure increases central excitation by selectively depressing inhibitory transmission per se; enhancement of potentiation, however, probably plays an important role. In this preparation, in which inhibitory transmission also displays facilitation, pressure did not increase overall excitation or alter the balance between excitation and inhibition. 5. These results predict that a pressure-excitable network should encompass excitatory synaptic connections which exhibit pronounced facilitation and inhibitory synapses with little or no facilitation.

Animals↗
PubMed1987

Cholinergic regulation of impulse frequency in peripheral nerve.

Previous studies have demonstrated the existence of receptors for gamma-aminobutyric acid (GABA), beta-adrenergic catecholamines and acetylcholine in vertebrate peripheral nerve, and provided functional correlates for activation of both GABA and beta-adrenergic receptors. The present studies show that a cholinergic receptor present on the nerve can also modify impulse pattern. In frog sciatic nerve, both carbamylcholine and dibutyryl cyclic GMP increased the amplitude of the response to the second stimulus of a train at very short interstimulus intervals. The effect of carbamylcholine was blocked by 4-aminopyridine. The results are consistent with the hypothesis that cholinergic agonists mediate an increase in endogenous cyclic guanosine monophosphate (cGMP), which increases the ability of the nerve to follow closely spaced stimuli by inhibiting potassium channels.

Action Potentials↗
PubMed1986

Pressure and temperature modulation of conduction in a bifurcating axon.

A bifurcating crustacean motor neuron, which serves an integrative function by selectively controlling output to its daughter branches, was examined for its behavioral response to changes in pressure and in temperature when each was varied while the other was held constant, and when both were varied together. The neuron was exposed to helium pressure between 1 and 200 ATA and temperatures between 9 and 22 degrees C. The response of the neuron to pressure changes was biphasic and time dependent. Immediately following a pressure change, action potential amplitude and conduction velocity increased, and the ability of the branch point to pass high frequency trains improved; after 15-20 min at pressures above 35 ATA these measures were depressed below control values. The curve relating functional measures to temperature displayed a time-dependent hysteresis, fast warming leading to values for amplitude, velocity, and branchpoint capacity which corresponded to those made at a point 3-5 degrees C higher during slow cooling. The delayed depressant effects of compression and cooling were synergistic. Low temperature significantly enhanced the effects of pressure on amplitude and conduction velocity; high pressure increased the Q10 of both measures. However, slow cooling antagonized the transient compression-induced excitability increase, and prolonged exposure to hyperbaric pressure diminished the temperature hysteresis. The complex time-dependent changes in this branching axon's ability to conduct are related to previously described changes in membrane potential properties. The responses of this axon to pressure changes are different from responses of other axons studied at hyperbaric pressure. Thus, even within relatively stereotyped axon membrane the effects of pressure are not generalizeable among cells. The possible relevance of these findings to the high pressure nervous syndrome (HPNS) is discussed.

Animals↗
PubMed1984

Ionic currents in vertebrate myelinated nerve at hyperbaric pressure.

To establish a base line for a study of anesthetic-pressure antagonism in axons, voltage-clamped nodes of Ranvier from amphibian sciatic nerve were subjected to pressures of 1-100 atm. Over the time of compression, there was usually an irreversible decrease in peak inward sodium current, but there was no change in peak outward sodium current or in the current-voltage relationship. The steady-state inactivation-voltage curve was shifted 5-15 mV in the depolarizing direction at 70-100 atm. The rate of rise of the sodium current was slowed, as was the time constant of inactivation (tau h). Increase in tau h was markedly voltage dependent, suggesting a selective effect of pressure on beta h, the rate constant governing development of the inactive state. The rate of development of steady-state outward potassium current was also decreased, without significant change in maximum current. The effects of pressure are qualitatively similar to, but different in detail from, those reported in squid axon and different in some details from the effects of cooling in this preparation. None of the effects can presently be related to the high-pressure nervous syndrome.

Animals↗
PubMed1984

Nitrogen narcosis and pressure reversal of anesthetic effects in node of Ranvier.

To compare sodium channel block by hyperbaric nitrogen with that induced by other anesthetics and to examine the basis for pressure antagonism to anesthetic condition block, voltage clamped nodes of Ranvier were exposed to nitrogen at pressures at 1-14 atm alone and in combination with helium to a total pressure of up to 100 atm. At 7 and 14 atm nitrogen, sodium currents were reversibly depressed without accompanying changes in the current-voltage relation. The curve relating steady-state inactivation (h infinity) to voltage was shifted in the hyperpolarizing direction, as is the case with other general anesthetic agents. The time constant of inactivation (tau h) was slightly decreased at depolarized potentials. The preceding companion paper demonstrated an opposite effect of hyperbaric helium on the properties of sodium inactivation. Addition of helium pressure in the presence of nitrogen at 14 atm did not increase peak sodium current with inactivation maximally removed, but it did shift the h infinity curve back toward control levels, thus increasing sodium current at points on the slope of the curve. It is proposed that these opposing shifts in steady-state inactivation levels are the basis for pressure antagonism to anesthetic conduction block. In the case of inert gases and volatile anesthetic agents, the antagonism may be direct but has not been shown to be so. In the case of the local anesthetic benzocaine, differences in the voltage dependence of anesthetic and pressure-induced changes in tau h indicate the antagonism is indirect.

Anesthesia, General↗
PubMed1984

Pressure and temperature: time-dependent modulation of membrane properties in a bifurcating axon.

A crustacean bifurcating motor neuron that selectively controls output to its daughter branches was exposed to helium pressure of 1-200 atmospheres (atm) and temperatures of 9-22 degrees C. The membrane responses of this integrative axon were monitored by intra- and extracellular recording, macropatch clamp, and Vaseline gap voltage clamp. The response of the neuron to pressure changes was biphasic and time dependent. Initially there was an increase in action potential amplitude and rate of rise, in magnitude of the inward sodium current, in conduction velocity, and in the ability of the branch point to conduct at high frequency. After 10-20 min at a given pressure above 35 atm, these functional measures declined to levels below control. Action potential duration increased throughout. In addition, membrane resting potential was depolarized by 10-15 mV, and input resistance increased. Pressure-related depolarization was not seen in an axon pretreated with ouabain, a result consistent with pressure inhibition of the electrogenic sodium pump in this axon. Cooling induced changes opposite to the initial effects and similar to the delayed effects of pressure in all measures, including action potential amplitude, rise time, duration, membrane potential, membrane resistance, inward current amplitude, conduction velocity, and ability to conduct at high frequency. This axon differs from other axons that have been studied at hyperbaric pressure in the bimodal nature of its response and in the magnitude of pressure-related depression of membrane properties related to excitability.

Animals↗
PubMed1983

Cyclic AMP reduction of frequency following ability in peripheral axons.

Radioimmunoassays for cAMP demonstrated that a beta-adrenergic agonist, isoproterenol, increased cAMP levels in isolated frog sciatic nerve. Dibutyryl cAMP (db-cAMP) and isoproterenol reduced the amplitude of the compound action potential and decreased the ability of the Xenopus sciatic nerve to follow high frequency stimulation. Similar effects of db-cAMP and a phosphodiesterase inhibitor were seen on intracellularly recorded action potentials of single lobster peripheral axons. These results suggest that cAMP can modulate the electrophysiological response properties of both myelinated and unmyelinated axons.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Barbiturates: active form and site of action at node of Ranvier sodium channels.

Barbiturate sodium channel block was investigated in the voltage-clamped amphibian node of Ranvier. Internal pH was manipulated by diffusion of buffers from the cut internodes. Like local anesthetics and volatile general anesthetics, barbiturates shift the voltage dependence of inactivation in the hyperpolarizing direction. A barbiturate anion, 5-phenyl barbituric acid, blocks sodium channels when applied externally or internally. On external application, block is of very slow onset. The barbiturate anion, like the local anesthetic cation, thus appears to bind to a receptor site on the axoplasmic side of the membrane. Unlike local anesthetics, however, phenobarbital exerts a frequency-dependent block which is modified by changes in internal pH and is not affected by changes in external pH. In addition, barbiturate frequency dependence is apparently more exclusively involved with channel inactivation. The results suggest a barbiturate sodium channel binding site closer to the axoplasm than the local anesthetic binding site is and also suggest that there is a proton barrier between the two sites.

Animals↗
PubMed1979

Nerve membrane lipid fluidity: opposing effects of high pressure and ethanol.

Studies on model phospholipid membranes have shown that general anesthetics and pressure exert opposing effects--anesthetics increase and high pressure decreases membrane fluidity. The present study extends these investigations to intact nerve membranes. The fluidity of the membranes of spin-labeled crayfish claw nerves was measured with electron paramagnetic resonance spectroscopy. Nerves exposed to 5- or 10% ethanol showed a linear increase in membrane fluidity. In contrast, 100 ATA of helium pressure decreased nerve fluidity. Successive application of ethanol and pressure to the nerve produced opposing effects. The similarity of effects between model and nerve membranes supports the relevance of studies with model systems.

Animals↗