SENSORY NEURON N-TYPE CALCIUM CURRENTS ARE INHIBITED BY BOTH VOLTAGE-DEPENDENT AND VOLTAGE-INDEPENDENT MECHANISMS

The voltage dependence of gamma-aminobutyric-acid- and norepinephrine- induced inhibition of N-type calcium current in cultured embryonic chi ck dorsal-root ganglion neurons was studied with whole-cell voltage-cl amp recording. The inhibitory action of the neurotransmitters was comp rised of at least two distinct modulatory components, which were separ able on the basis of their differential voltage dependence. The first component, which we term ''kinetic slowing'', is associated with a slo wing of the activation kinetics - an effect that subsides during a tes t pulse. The kinetic-slowing component is largely reversed at depolari zed voltages (i.e., it is voltage-dependent). The second component, wh ich we term ''steady-state inhibition'', is by definition not associat ed with a change in activation kinetics and is present throughout the duration of a test pulse. The steady-state inhibition is not reversed at depolarized voltages (i.e., it is voltage-independent). Although th e two components can be separated on the basis of their voltage depend ence, they appear to be indistinguishable in their time courses for on set and recovery as well as their rates of desensitization following m ultiple applications of transmitter. Furthermore, neither component re quires cell dialysis, as both are observed using perforated-patch as w ell as whole-cell recording configurations. The co-existence in nerve terminals of both voltage-dependent and -independent mechanisms to mod ulate calcium channel function could offer a means of differentially c ontrolling synaptic transmission under conditions of low- and high-fre quency presynaptic discharge.