Spatial distribution of Ca currents in molluscan neuron cell bodies and regional differences in the strength of inactivation

Abstract

The spatial distribution of Ca current in molluscan neuron cell bodies was studied using a large patch method in combination with 2-microelectrode voltage clamp. The method has a spatial resolution equal to about 0.1% of the cell body area. Ca current is not uniformly distributed. The current density varies between patches, changing by as much as a factor of 2.5 over a distance of 20 micron, and there is evidence that Ca current occurs in "hot spots" involving a few hundred channels. The current density increases in a moderately steep gradient from the soma cap, opposite the axon, toward the axon hillock. Ca currents in patches from different regions of the soma are qualitatively different. Currents near the soma cap do not inactivate or inactivate weakly during depolarization, while currents of equal density nearer the axon hillock exhibit pronounced inactivation. The strength of inactivation increases in parallel with the gradient in current density, but local differences in current density, or in the number of active Ca channels, do not explain the variability in inactivation. Inactivating and noninactivating Ca currents could not be distinguished on the basis of activation or deactivation kinetics, voltage dependence of activation, or sensitivity to hyperpolarizing conditioning pulses. Also, the amplitude of noninactivating current near the soma cap is reduced by intracellular Ca injection showing that, like the whole-cell current, Ca current in this region is subject to Ca-dependent inactivation. The data favor the hypothesis that these cells express only one type of Ca channel. Differences in the strength of inactivation may result from local differences in cytoplasmic Ca buffering, local modification of Ca channels in a way that changes their sensitivity to Ca-dependent inactivation, or local differences in the availability of cytoplasmic factors or enzymes that are necessary for inactivation.