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Biomedical subjects

R Werman

Publications and source records attributed to R Werman.

At least 37 records · Page 2Linked to original sources
PubMed1978

EGTA and motoneuronal after-potentials.

1. Intracellular iontophoretic injections of EGTA (5--20 nA) into cat spinal motoneurones consistently greatly reduce the amplitude of the delayed after hyperpolarization (a.h.p.) that follows the spike. 2. This effect is accompanied by a large reduction (on average by 3/4) in the marked increase in input conductance normally associated with the a.h.p. 3. There is also a consistent, though less regular, tendency for the resting input conductance to decrease (on average by 1/5), as well as some depolarization. 4. Recovery of the a.h.p., the associated conductance increase and the resting conductance is ver slow. It is sometimes accelerated by injections of citrate and Cl-, or CA2+. 5. Other hyperpolarizing phenomena, such as recurrent or othodromically-evoked i.p.s.p.s, are not depressed by injections of EGTA. 6. When depolarization is minimal EGTA injections that markedly depress the a.h.p. do not affect the rate of rise or fall of the spike. If, as a result of depolarization, an early a.h.p. is visible, it is patently insensitive to EGTA. 7. The post-spike depolarizing after-potential (delayed depolarization) is not obviously affected by EGTA, apart from the usual diminution seen during depolarization. 8. Since the main action of EGTA is to bind free Ca2+, the marked depression of the a.h.p. indicates that the sharp increase in K conductance which generates the a.h.p. is probably caused by a influx of Ca2+ accompanying the action potential. It is suggested that this inward Ca2+ current may be manifested in the depolarizing after-potential.

Action Potentials↗
PubMed1978

Significance of 2,4-dinitrophenol action on spinal motoneurones.

1. Extracellular iontophoretic applications of DNP lead to an increase in the membrane conductance of cat spinal motoneurones, manifested by a rise in input conductance, a slower rate of rise and fall of action potentials, and occlusion of the afterhyperpolarization. 2. There is also some hyperpolarization, but the reversal potential for the action of DNP is only about 12 mV more negative than the resting potential. 3. These effect of DNP can be abolished or significantly reduced by intracellular injections of EGTA. On the other hand, DNP can partly reverse the decreased conductance and the depression of the slow afterhyperpolarization caused by EGTA. 4. Intracellular injections of DNP also induce a rise in input conductance; when repeated, they tend to have a depolarizing effect, mainly irreversible. 5. It is concluded that DNP acts principally inside the motoneurone, by liberating bound internal Ca, the free Ca ions then raising membrane conductance, especially GK.

Action Potentials↗
PubMed1977

GABA and glycine actions on spinal motoneurons.

Applied microiontophoretically in the spinal cord of cats, glycine is consistently more powerful than gamma-aminobutyric acid (GABA) in raising the membrane conductance of lumbosacral motoneurons (mean ratio of equipotent iontophoretic currents tested on same cells is 5.6:1). This is the reverse of the situation in cerebral cortex. The effect of glycine is well maintained during applications lasting about 1 min, but that of GABA, after an early peak, drops to a much lower plateau (mean plateau-over-peak ratio is 0.23). The reversal potentials for the action of GABA and glycine are initially similar but they behave differently during a prolonged application; that for glycine usually remains constant or becomes more negative whereas that for GABA tends to shift in the positive direction. Various explanations of these phenomena are considered. It is suggested that a single process, electrogenic uptake of GABA, may account for both desensitization (by removing GABA from its site of action) and the positive shift in GABA reversal potential (became uptake is probably associated with an influx of Na+).

Action Potentials↗
PubMed1977

Bicuculline, benzyl penicillin, and inhibitory amino acids in the spinal cord of the cat.

Bicuculline methochloride (BMC), applied by microiontophoresis, tends to depolarize spinal motoneurons and lower their input resistance. With approximately equal iontophoretic currents of gamma-aminobutyric acid (GABA) and BMC, there is an almost equal chance of observing no change, a potentiation, or a depression of the GABA-evoked conductance increase. A block of the GABA action is seen consistently only when the iontophoretic current of BMC is at least double that of GABA. Under these conditions BMC can selectively antagonize GABA without blocking the effects of glycine, though the latter can also be blocked by larger amounts of BMC. BMC also regularly eliminates the usual apparent desensitization to GABA. This may be due to depression of GABA uptake by BMC, which would also account for its potentiating action at lower relative doses. Comparable effects are observed with iontophoretic applications of benzyl penicillin (BP); but even large doses of BP produce no definite change in membrane properties or in conductance increase evoked by GABA or glycine.

Action Potentials↗
PubMed1976

The thiol-oxidizing agent diamide increases transmitter release by decreasing calcium requirements for neuromuscular transmission in the frog.

Diamide, which in concentrations of 10(-5) M and higher oxidizes glutathione intracellularly, produces a dose-related increase in the frequency of miniature end-plate potentials (MEPPs). With high enough doses, quantal release is blocked, apparently through exhaustion. The early phase of MEPP frequency increase is accompanied by an increase in EPP amplitude that may reach more than 10-fold and is therefore not produced by depolarization of axon terminals. Subsequently, EPP amplitude is reduced and falls to zero, associated with failure of invasion of the nerve action into the terminals while the MEPP frequency remains elevated. Both facilitation and PTP follow the time course of change in EPP amplitude. The increase in MEPP frequency with diamide does not require external Ca2+ but raising external Ca2+ increases the MEPP rate in the presence of diamide. External Ca2+ is necessary for EPP appearance and also potentiates the diamide effects. Conversely diamide reduces the requirements for Ca2+ in releasing ACh. Diamide substitutes for external Ca2+ in K+ evoked MEPP release and in the absence of external Ca2+, diamide-evoked MEPP release is increased by raising external Mg2+ levels. The action of diamide may be dependent on the actual release of Ca2+ from intracellular stores or it may work through mimicking some of the actions of Ca2+. The action of diamide bears close resemblance to the effects of prolonged stimulation of the motor axon at 10 Hz.

Acetylcholine↗
PubMed1976

Diamide acts intracellularly to enhance transmitter release: the differential permeation of diamide, DIP, DIP+1 and DIP+2 across the nerve terminal membrane.

The actions of the new potent thiol oxidizing agents, diazene dicarboxylic acid bis (N'-methyl piperazide) (DIP) and the N'-methyl iodide (DIP + 1) and the bis-N'-methyl iodide (DIP + 2) salts of DIP, were tested at the frog neuromuscular junction. At 20 degrees C, DIP was as fast as the thiol oxidizing agent, diamide, in evoking transmitter release but was appreciably less effective at 6 degrees C. DIP + 1 and DIP + 2 did not increase transmitter release. Since the three agents are potent oxidizers of glutathione and since the effectiveness of the compounds appears to depend on their ability to exist, at least in part, in a neutral form at physiological pH, it is concluded that their action as promoters of transmitter release depends on their ability to permeate nerve terminal membranes. Thus, both diamide and DIP act to increase transmitter release by the intracellular oxidation of glutathione. The two charged agents, DIP + 1 and DIP + 2, are potent muscular depolarizing agents. It is probable that the quaternary nitrogen groups of these compounds render them cholinomimetics.

Acetylcholine↗
PubMed1976

Penicillin decreases chloride conductance in crustacean muscle: a model for the epileptic neuron.

The effects of penicillin were studied on the neuromuscular preparation of the ghost crab, Ocypoda cursor. Penicillin in doses lower than 2 mM reduced both the amplitude of inhibitory junction potentials and conductance increases induced by external application of GABA. The nature of the latter effect appears to be 2-fold, a weaker competitive inhibition and a more powerful non-competitive effech which may be ionophore blockade. Penicillin in concentrations above 2 mM diminished resting conductance, especially that of chloride. The action of penicillin is, in general, to decrease chloride conductance in this preparation. The crustacean neuromuscular preparation may provide a useful analogue for understanding penicillin evoked epilepsy. The reduced chloride conductance could explain decreased inhibition, increased excitation and depolarization shifts in cortical neurons.

Animals↗
PubMed1976

The physiology and anatomy of long ranging afferent fibres within the spinal cord.

The caudal extent of the terminal arborizations of dorsal root afferents was determined in adult cats. The method used micro-electrode stimulation within the dorsal horn and the recording on a distant dorsal root filament of the antidromic action potentials evoked by the stimulation of axons within the spinal cord. 2. It was found that all filaments examined in the L2, 3 and 4 dorsal roots contained axons which projected at least as far as the S1 segment. The axons descended in or near the dorsal columns and from there penetrated into the grey matter. 3. The course of single fibres was followed to their apparent terminals. Thresholds, latencies and relative and absolute refractory periods were measured for single axons. These measurements confirmed that continuous axons ran from dorsal roots to distant segments and that the action potentials recorded were not dorsal root reflexes. 4. The majority of fibres with long range central arborizations were shown to have normal receptive fields in the dermatome of their parent dorsal root. They were not aberrant fibres leaving the spinal cord. 5. The long range afferents exist in substantial numbers since fifteen of eighty axons isolated by micro-electrode recording in the L2 dorsal root sent their axons as far as the S1 segment. The presence of these afferents from five segments away does not fit the data published on the inhibitory and excitatory receptive fields or dorsal horn cells which appear adequately explained by afferents arriving over nearby dorsal roots up to two segments away.

Action Potentials↗
PubMed1976

Intracellular Mg2+ increases neuronal excitability.

Injection of Mg2+ into spinal motoneurons of cats leads to a depolarization, associated with a fall in membrane conductance, diminution in post-spike hyperpolarization, and increased excitability. This action has an apparent reversal level substantially more negative than the resting potential, and can be ascribed to a fall in K+ membrane conductance. Since these effects are opposite to those produced by intracellular Ca2+, it is suggested that Mg2+ probably competes with Ca2+ at the Ca2+-activated K+ ionophoreal free ionophores. Neuronal excitability can be regulated by the ratio of internal free Ca2+/Mg2+.

Animals↗
PubMed1976

Is cyclic guanosine monophosphate the internal 'second messenger' for cholinergic actions on central neurons?

The most consistent effects produced by intracellular injections of guanosine 3',5'-cyclic monophosphate (cGMP) (but not 5'-guanosine 5'-monophosphate in spinal motoneurons of cats are a rise in membrane conductance, acceleration in time course of spike potentials, and accentuation of the post-spike hyperpolarization. Associated changes in resting potential are smaller, less constant, and more often in the depolarizing than hyperpolarizing direction, cGMP tends to increase electrical excitability but reduces excitatory post-synaptic potential amplitudes. Most of the effects of intracellular cGMP are quite different from, or indeed opposite to, those of either extra- or intracellular applications of acetylcholine and therefore not consistent with the proposal that cGMP is the internal mediator of muscarinic actions.

Acetylcholine↗