Effects of protein kinase C inhibitor H-7 on membrane properties and synaptic responses of neocortical neurons of awake cats.

Electrophysiological effects of intracellularly pressure-injected H-7, an inhibitor of protein kinase C, were investigated in neocortical neurons of awake cats. H-7 reduced spontaneous and depolarizing current-induced firing activity and increased the latency and apparent threshold of action potentials elicited by depolarizing currents. Slow afterhyperpolarizations following action potentials and depolarizing pulses increased after injection of H-7, without detectable changes in the time course of the fast components of the action potentials. H-7 induced increases in IPSPs evoked by stimulation of the ventrolateral thalamus (VL) or the pyramidal tract (PT). Besides slight increases in the amplitude of IPSPs measured at peak, H-7 induced pronounced increases in the amplitude measured 50-100 ms after stimulation and in the total duration of IPSPs. EPSPs evoked by VL or PT stimulation did not show measurable alterations after injection of H-7. The effects occurred 2-15 min after injection of H-7 and lasted at least 90 min without essential changes in the baseline values of resting membrane potential or input resistance. The results suggest that in addition to playing a role in regulating membrane excitability, protein kinase C influences the inhibitory synaptic mechanisms of neocortical neurons.