Biomedical subjects

A B MacDermott

Publications and source records attributed to A B MacDermott.

39 records · Page 3Linked to original sources

PubMed1980

Voltage clamp study of fast excitatory synaptic currents in bullfrog sympathetic ganglion cells.

Excitatory postsynaptic currents (EPSCs) have been studied in voltage-clamped bullfrog sympathetic ganglion B cells. The EPSC was small, rose to a peak within 1-3 ms, and then decayed exponentially over most of its time-course. For 36 cells at --50 mV (21-23 degrees C), peak EPSC size was --6.5 +/- 3.5 nA (mean +/- SD), and the mean decay time constant tau was 5.3 +/- 0.9 ms. tau showed a small negative voltage dependence, which appeared independent of temperature, over the range --90 to --30 mV; the coefficient of voltage dependence was --0.0039 +/-0.0014 mV-1 (n = 29). The peak current-voltage relationship was linear between --120 and --30 mV but often deviated from linearity at more positive potentials. The reversal potential determined by interpolation was approximately --5 mV. EPSC decay tau had a Q10 = 3. The commonly used cholinesterase inhibitors, neostigmine and physostigmine, exhibited complex actions at the ganglia. Neostigmine (1 X 10(-5)M) produced a time-dependent slowing of EPSC decay without consistent change in EPSC size. In addition, the decay phase often deviated from a single exponential function, although it retained its negative voltage dependence. With 1 x 10(-6) M physostigmine, EPSC decay was slowed by the decay phase remained exponential. At higher concentrations of physostigmine, EPSC decay was markedly prolonged and was composed of at least two decay components. High concentrations of atropine (10(-5) to 10(-4) M) produced complex alterations in EPSC decay, creating two or more exponential components; one decay component was faster and the other was slower than that observed in untreated cells. These results suggest that the time-course of ganglionic EPSC decay is primarily determined by the kinetics of the receptor-channel complex rather than hydrolysis or diffusion of transmitter away from the postsynaptic receptors.

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PubMedDate not supplied

Detection of intracellular Ca2+ transients in sympathetic neurones using arsenazo III.

Changes in cytosolic calcium ion concentration ([Ca2+]i) have been implicated in a wide variety of cellular stimulus--transduction roles. In nerve cells, it is believed that electrical activity raises [Ca2+]i by allowing influx of Ca2+ through voltage-dependent channels in the surface membrane. Elevation of neuronal [Ca2+]i may also occur due to release of Ca2+ from intracellular storage sites. Transient increases in [Ca2+]i are thought to trigger neurotransmitter release, and to modulate axonal transport, energy metabolism and growth cone movement. Intracellular Ca2+ also appears to regulate membrane potassium channels and thereby to regulate electrical excitability. Although [Ca2+]i transients have been measured in a few giant invertebrate neurones, detection of such transients in a vertebrate neurone has not been previously reported. We have measured [Ca2+]i in bullfrog sympathetic neurones by photometry of a microinjected calcium indicator dye, arsenazo III (refs 14-16), and report here that action potentials and voltage-clamped depolarizations cause long-lasting increases in [Ca2+]i. Aslo, exposure to the drug theophylline can cause spontaneous periodic increases in [Ca2+]i. Comparisons of [Ca2+]i signals with simultaneous intracellular recordings of membrane potential suggest that the kinetics of the post-tetanic hyperpolarization (PTH) following a series of action potentials or the spontaneous hyperpolarizations induced by theophylline directly reflect the kinetics of the [Ca2+]i transient.

Action Potentials↗

PubMedDate not supplied

NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones.

Excitatory amino acids act via receptor subtypes in the mammalian central nervous system (CNS). The receptor selectively activated by N-methyl-D-aspartic acid (NMDA) has been best characterized using voltage-clamp and single-channel recording; the results suggest that NMDA receptors gate channels that are permeable to Na+, K+ and other monovalent cations. Various experiments suggest that Ca2+ flux is also associated with the activation of excitatory amino-acid receptors on vertebrate neurones. Whether Ca2+ enters through voltage-dependent Ca2+ channels or through excitatory amino-acid-activated channels of one or more subtype is unclear. Mg2+ can be used to distinguish NMDA-receptor-activated channels from voltage-dependent Ca2+ channels, because at micromolar concentrations Mg2+ has little effect on voltage-dependent Ca2+ channels while it enters and blocks NMDA receptor channels. Marked differences in the potency of other divalent cations acting as Ca2+ channel blockers compared with their action as NMDA antagonists also distinguish the NMDA channel from voltage-sensitive Ca2+ channels. However, we now directly demonstrate that excitatory amino acids acting at NMDA receptors on spinal cord neurones increase the intracellular Ca2+ activity, measured using the indicator dye arsenazo III, and that this is the result of Ca2+ influx through NMDA receptor channels. Kainic acid (KA), which acts at another subtype of excitatory amino-acid receptor, was much less effective in triggering increases in intracellular free Ca2+.

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