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Biomedical subjects

M L Mayer

Publications and source records attributed to M L Mayer.

At least 91 records · Page 5Linked to original sources
PubMed1985

A calcium-activated chloride current generates the after-depolarization of rat sensory neurones in culture.

Neurones from the dorsal root ganglia of 1-day-old rat pups were grown in dissociated culture and voltage clamped using patch electrodes for whole-cell recording. The pipettes were filled with either 140 mM-KCl or CsCl. Depolarizing voltage jumps activated net inward calcium currents in all neurones, which in a subpopulation of 46% were followed by slowly decaying inward tail currents accompanied by large increases in membrane conductance. During voltage jumps to membrane potentials more positive than 0 mV the inward calcium current was contaminated by a slow outward relaxation only in those neurones with slow inward tail currents. The availability curve for the slow inward tail current was U shaped, with a peak at approximately +5 mV in medium containing 2.5 mM-Ca2+; further depolarization reduced the amplitude of the tail current. During perfusion with calcium-free solution, or in the presence of the calcium-channel blockers cadmium or cobalt, or on substitution of barium for calcium, both the slow inward tail currents and outward relaxations were reversibly blocked. The reversal potential of the slow inward tail current, measured using a twin-pulse protocol, was approximately -10 mV. Replacement of sodium by tetraethylammonium (TEA) did not reduce the slow inward tail current, nor change its reversal potential. Reduction of the extracellular chloride activity produced a large increase in the amplitude of the slow inward tail current suggesting an increase in permeability to anions. This conductance, which behaves as though activated by prior or concurrent calcium entry triggered by membrane potential depolarization, is referred to as ICl(Ca). The activation and deactivation kinetics of ICl(Ca) are complex: envelope experiments measuring peak tail current amplitude revealed activation to be described by a single exponential function, of time constant approximately 100 ms at -10 to +8 mV. The integral of the tail currents increased with the duration of depolarizing pre-pulses suggesting accumulation of intracellular calcium. The decay of tail currents activated by short depolarizing voltage jumps was described by a single exponential function of time constant approximately 200 ms at -60 mV; more complex decay kinetics were recorded following activation by voltage jumps of duration greater than 60 ms. Tail current decay was voltage sensitive, becoming faster with hyperpolarization and increasing e-fold per 120 mV change in membrane potential.

Action Potentials↗
PubMed1984

Mg2+ dependence of membrane resistance increases evoked by NMDA in hippocampal neurones.

The response of granule cells and CA1 pyramidal neurones to NMDA was studied in the presence and absence of Mg2+ using an in vitro slice preparation. In the absence of Mg2+ the depolarizing response of hippocampal neurones to NMDA is accompanied by a decrease in input resistance. In the presence of Mg2+ ions, however, the response to NMDA is always associated with an apparent increase in input resistance. These results indicate that the action of NMDA is by a classical mechanism of conductance increase and are in agreement with the suggestion that the apparent increase in input resistance associated with NMDA depolarizations is the result of voltage-dependent channel block by Mg2+ of the NMDA evoked current.

Animals↗
PubMed1984

Glutamate currents in mammalian spinal neurons: resolution of a paradox.

Mouse spinal cord neurons grown in tissue culture were impaled with a pair of microelectrodes containing 1 M CsCl and voltage-clamped. Membrane currents evoked by excitatory amino acids were studied over the potential range -70 to +20 mV. Glutamate currents behaved as though generated by simultaneous activation of two conductance mechanisms, one voltage-sensitive, the other conventional. Block of NMDA receptors with the competitive antagonist 2-APV removed the voltage-sensitive component of the glutamate response. These results help to explain the paradoxical lack of conductance-change previously reported for glutamate responses recorded in the mammalian CNS.

Animals↗
PubMed1984

Lithium ions increase action potential duration of mammalian neurons.

During Lucifer Yellow staining of mammalian neurons, intracellular recording revealed a prolongation of the action potential that is probably the result of leakage of lithium ions into the intracellular fluid. In experiments on dorsal root ganglion neurons intracellular iontophoresis of lithium ions also broadened the action potential. Cadmium, a calcium channel blocker, shortens the lithium-evoked wide actions potentials. The present experiments do not reveal whether lithium directly enhances inward calcium current, or whether a block of outward rectification allows calcium currents to increase the action potential duration.

Action Potentials↗
PubMed1984

Mixed-agonist action of excitatory amino acids on mouse spinal cord neurones under voltage clamp.

Neurones from the ventral half of mouse embryo spinal cord were grown in tissue culture and voltage clamped with two micro-electrodes. The current-voltage relation of responses evoked by brief pressure applications of excitatory amino acids was examined over a membrane potential range of -100 to +70 mV. Three types of current-voltage relation were observed. Responses to kainic and quisqualic acids were relatively linear within +/- 20 mV of the resting potential. N-methyl-D-aspartate (NMDA) and L-aspartic acid responses had a negative slope conductance at membrane potentials more negative than -30 mV. In contrast, over the same potential range the slope conductance of responses evoked by L-glutamic and L-homocysteic acids was close to zero. The membrane potential-chord conductance relation of the ionic mechanism activated by excitatory amino acids, derived using the driving force for ionic current, showed two types of behaviour. The conductance linked to NMDA receptors was highly voltage sensitive and increased on depolarization; a much weaker voltage sensitivity was observed for responses evoked by kainic and quisqualic acids. L-glutamic and L-homocysteic acid responses behaved as though due to simultaneous activation of both NMDA and either kainate or quisqualate receptors. In the presence of the NMDA receptor antagonist (+/-)-2-aminophosphonovaleric acid (2-APV) the response to L-glutamate became less voltage sensitive and resembled responses evoked by kainate or quisqualate. Simultaneous activation of both conductance mechanisms by mixtures of kainate and NMDA produced current-voltage and membrane potential-chord conductance relations similar to those of L-glutamate. The voltage sensitivity of the L-glutamate response was inversely related to the dose; for low doses of L-glutamate the slope conductance of responses recorded near the resting potential was close to zero. However, larger doses of L-glutamate evoked responses with a voltage sensitivity similar to that of kainate. We suggest that L-glutamate acts as a mixed agonist at both NMDA and non-NMDA receptors. This can explain the results of previous experiments that failed to demonstrate a membrane resistance change during L-glutamate-induced depolarizations.

2-Amino-5-phosphonovalerate↗
PubMed1983

On the mechanism of action of GABA in pelvic vesical ganglia: biphasic responses evoked by two opposing actions on membrane conductance.

Intracellular recording techniques were used to study the response of cat vesical pelvic ganglion neurones loaded with permeable anions to the application of GABA in vitro. In 106/127 neurones GABA evoked a biphasic response, the initial phase of which was depolarizing and associated with a conductance increase; the latter phase was hyperpolarizing and associated with a conductance decrease. The GABA evoked hyperpolarization and conductance decrease were related and behaved as though generated by closure of ion channels open in the resting membrane. The hyperpolarization had a strong inhibitory action on both spontaneous activity, and excitation evoked by depolarizing current injection and pre-synaptic nerve stimulation. Ion substitution experiments suggest that the conductance decrease is primarily to chloride ions, although other ionic species may contribute. Short iontophoretic applications of GABA-evoked monophasic depolarizing excitatory responses, even during the hyperpolarizing response evoked by perfusion of GABA, suggesting no cross-desensitization between the mechanisms generating the initial and late phases of the biphasic response.

Animals↗
PubMed1983

A voltage-clamp analysis of inward (anomalous) rectification in mouse spinal sensory ganglion neurones.

Mouse embryo dorsal root ganglion neurones were grown in tissue culture and voltage-clamped with two micro-electrodes. Hyperpolarizing voltage commands from holding potentials of -50 to -60 mV evoked slow inward current relaxations which were followed by inward tail currents on repolarization to the holding potential. These relaxations are due to the presence of a time- and voltage-dependent conductance provisionally termed Gh. Gh activates over the membrane potential range -60 to -120 mV. The presence of Gh causes time-dependent rectification in the current-voltage relationship measured between -60 and -120 mV. Gh does not inactivate within this range and thus generates a steady inward current at hyperpolarized membrane potentials. The current carried by Gh increases when the extracellular K+ concentration is raised, and is greatly reduced in Na+-free solutions. Current-voltage plots show considerably less inward rectification in Na+-free solution; conversely inward rectification is markedly enhanced when the extracellular K+ concentration is raised. The reversal potential of Ih is close to -30 mV in media of physiological composition. Tail-current measurement suggests that Ih is a mixed Na+-K+ current. Low concentrations of Cs+ reversibly block Ih and produce outward rectification in the steady-state current-voltage relationship recorded between membrane potentials of -60 and -120 mV. Cs+ also reversibly abolishes the sag and depolarizing overshoot that distort hyperpolarizing electrotonic potentials recorded in current-clamp experiments. Impermeant anion substitutes reversibly block Ih; this block is different from that produced by Cs+ or Na+-free solutions: Cs+ produces outward rectification in the steady-state current-voltage relationship recorded over the Ih activation range; in Na+-free solutions inward rectification, of reduced amplitude, can still be recorded since Ih is a mixed Na+-K+ current; in anion-substituted solutions the current-voltage relationship becomes approximately linear. It is concluded that in dorsal root ganglion neurones anomalous rectification is generated by the time-and voltage-dependent current Ih. The possible function of Ih in sensory neurones is discussed.

Action Potentials↗
PubMed1981

A barbiturate evoked intensification of postsynaptic inhibition in the preoptic ovulatory trigger region of the hypothalamus.

Extracellular single unit recordings were used to study inhibitory synaptic responses evoked from preoptic-anterior hypothalamic neurones following arcuate-ventromedial stimulation. Intravenously administered methohexitone, pentobarbitone and thiopentone increased the duration of inhibitory synaptic responses by up to 400%. Submaximal responses to iontophoretically applied GABA but not glycine were also potentiated. Recovery from the actions of the short acting barbiturates was observed.

Animals↗
PubMed1981

Inhibitory actions of amino acids in the preoptic-anterior hypothalamus of the rat.

Extracellular recordings were made from preoptic-anterior hypothalamic neurones with combined recording and iontophoresis electrodes. Short iontophoretic applications of beta-alanine, GABA, glycine and taurine inhibited the discharge of the majority of neurones tested. Bicuculline metho-chloride reversibly and selectively antagonised GABA responses. Strychnine reversibly antagonised beta-alanine, glycine and taurine but not GABA responses. These results suggest the existence of two populations of inhibitory amino acid receptors in the preoptic-anterior hypothalamus. The function of inhibitory amino acids in the rostral hypothalamus was briefly discussed.

Amino Acids↗
PubMed1981

Electrophysiological analysis of inhibitory synaptic mechanisms in the preoptic area of the rat.

1. Extracellular recordings were made from single neurones in the medial preoptic-anterior hypothalamus of rats anaesthetized with urethane or pentobarbitone 2. Stimulation of the arcuate--ventromedial area evoked inhibition in 76% of neurones; inhibition occurred as the initial response in 26% of neurones, followed orthodromic excitation in 26% and antidromic excitation in 24%. Stimulation of the periaqueductal grey evoked inhibition as the initial response in 63% of neurones. 3. Stimulation of both the arcuate--ventromedial area and the periaqueductal grey generated synaptically evoked high-frequency discharges in a few neurones. 4. Short ionophoretic pulses of beta-alanine, gamma-aminobutyric acid (GABA), glycine and taurine inhibited the discharge of most preoptic-anterior hypothalamic neurones. Bicuculline methochloride and picrotoxin antagonized both GABA responses and synaptic inhibition. Strychnine antagonized beta-alanine, glycine and taurine responses without altering synaptic inhibition. 5. Reduction of hypothalamic serotonin (5-HT) levels to about 40% of control values by micro-injection of 5,7-dihydroxytryptamine into the ventral tegmental area, or parenteral injection of parachlorophenylalanine, did not alter the profile of responses evoked by either arcuate-ventromedial or periaqueductal grey stimulation. Micro-injection of tetanus toxin (100-200 MLD) into the preoptic-anterior hypothalamus significantly reduced the frequency of occurrence of inhibition evoked from both sites. 6. Pentobarbitone administered acutely or as the sole anaesthetic increased both the duration and frequency of occurrence of inhibitory responses evoked from the arcuate-ventromedial nuclei. 7. It is suggested that a GABA-linked inhibitory synaptic mechanism, activated by arcuate-ventromedial and periaqueductal grey stimulation, operates in the preoptic-anterior hypothalamus. Such convergent inhibition may be a result of activity in local interneurone circuitry.

Animals↗
PubMed1980

Electrophysiological analysis of pathways connecting the medial preoptic area with the mesencephalic central grey matter in rats.

1. An electrophysiological study of ascending and descending connexions between the dorsal raphe region of the mesencephalic periaqueductal grey matter and the medial preoptic area has been performed in dioestrous female rats anaesthetized with urethane. 2. Extracellular action potentials recorded from 208 neurones in the medial preoptic area were analysed for a change in excitability following stimulation of the periaqueductal grey matter. 174 neurones were also tested for changes in excitability following stimulation of the mediobasal hypothalamus. 3. Stimulation of the periaqueductal grey matter at 1 Hz was rarely effective, but short trains of pulses (three at 100 Hz) usually caused an initial inhibition (62.5% of 208) of both projection identified and adjacent neurones of the medial preoptic area, at latencies of 5--90 msec (mean 34.1 +/- 1.4 msec). Inhibition following stimulation of the mediobasal hypothalamus occurred less frequently (34%) and at shorter latency (mean 12.0 +/- 1.8 msec; n = 48). 4. Less frequently (10.6%) periaqueductal grey matter stimulation caused an initial excitation of preoptic neurones at latencies of 15--180 msec, (mean 35.3 +/- 7.2). Initial excitation following mediobasal hypothalamus stimulation was stronger, occurred more frequently (29%) and at shorter latencies (range 3--60 msec, mean 13.1 +/- 1.5). Following such initial excitation, inhibition of spontaneous or ionophoretically evoked activity occurred more frequently following mediobasal hypothalamic stimulation, than after periaqueductal grey matter stimulation. 5. Twenty-four neurones displayed antidromic invasion following periaqueductal grey matter stimulation. Latencies for invasion ranged from 13 to 50 msec (mean 25.5 +/- 2.0 msec) and are suggestive of an unmyelinated projection. Occasionally an abrupt decrease in latency followed an increase in stimulus intensity. Antidromic invasion from mediobasal hypothalamus was characterized by a shorter latency (mean 12.5 +/- 0.7 msec; n = 43). A period of reduced excitability lasting 40--100 msec followed antidromic invasion from either site. 6. Antidromic responses to paired mediobasal hypothalamic or periaqueductal grey matter stimuli at 5 msec intervals revealed an increased latency of invasion of the second response, due to the partial refractory period of the neurone. Five cells showed a decreased latency of invasion at stimulus separations of 10--150 msec, interpreted as evidence of a supranormal period. Changes in conduction velocity during the supranormal period may give rise to a variable latency of invasion of spontaneously active cells. 7. These results provide evidence for direct, reciprocal connexions between the midbrain central grey and the medial preoptic area. These circuits may play a role in controlling neuroendocrine and behavioural aspects of reproductive functions.

Action Potentials↗