Electrophysiological study of GABAA versus GABAB receptors on excitation-secretion coupling.
Inwardly-directed Ca++-currents are caused by numerous types of action potentials which would not otherwise cause secretion. This process is regulated electrically and by neurotransmitters. We have studied in vitro the ionic mechanisms of GABA-mediated presynaptic inhibition and thereby the distinctive characteristics of GABAA and GABAB receptors: i.e., the GABAA system, which produces such short-lasting changes that there is an instantaneous reduction of spike amplitudes, in particular by opening Cl- -conductance, and the GABAB system, which results directly in inhibition of secretion due to a tonic depression of Ca++-currents. The principal aim was to determine if GABAB/Ca++ receptors could coexist on a membrane already possessing a large number of GABAA/Cl- sites available for presynaptic inhibition. Intracellular recordings of A delta and C dorsal root ganglion cell bodies were used as a model for the study of preterminal axonal membranes. Results were tentatively correlated with those obtained extracellularly by recording Ca++ and K+ movements (Cl- being assessed indirectly) from a set of other cells which also secrete neuropeptides by exocytosis: e.g., endings of unmyelinated fibres in the neurohypophysis and clusters of innervated gland cells in the pars intermedia. In recent years there has been a growing interest in receptors for neurotransmitters (e.g., monoamines, peptides, gamma-aminobutyric acid) modulating Ca++-dependent secretion in various biological systems (14-16, 24, 25, 29, 34). Modulation is possible either by changing the basic characteristics of the ionic currents during a standard action potential (Na+/K+ voltage transients being markedly altered by repolarizing K+ currents) or by any kind of direct action on voltage-dependent Ca++-channels: the latter will allow Ca++ to enter the cell in graded amounts not only as parts of well-defined Ca++-spikes (16, 14, 39; see also 24, 26, 28) but of well-defined Ca++-spikes (16, 14, 39; see also 24, 26, 28) but possibly also along complex sequences of tail-currents (for the biophysics, see 28, 29). Accordingly, it is essential to study presynaptic actions of transmitters in systems where spikes can be recorded, though presynaptic receptor activation can sometimes be identified by other means than spiking patterns (e.g., membrane effects in relation to other well-defined ionophores). The study of cells which are in contact with synapses synthesizing and releasing gamma-aminobutyric acid (GABA) has drawn much of the attention given to these problems.(ABSTRACT TRUNCATED AT 400 WORDS)
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000502:physiology; D004594:Electrophysiology; D005724:Ganglia / Q000502:physiology; D009424:Nervous System Physiological Phenomena; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D011963:Receptors, GABA-A; D013569:Synapses / Q000502:physiology; D013570:Synaptic Membranes / Q000502:physiology
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D002118:Calcium