A zinc-dependent Cl- current in neuronal somata

Extracellular Zn2+ modulates current passage through voltage- and neurotran smitter-gated ion channels, at concentrations less than, or near, those pro duced by release at certain synapses. Electrophysiological effects of cytop lasmic Zn2+ are less well understood, and effects have been observed at con centrations that are orders of magnitude greater than those found in restin g and stimulated neurons. To examine whether and how neurons are affected b y lower levels of cytoplasmic Zn2+, we tested the effect of Zn2+-selective chelators, Zn2+ preferring ionophores, and exogenous Zn2+ on neuronal somat a during whole-cell patch-clamp recordings. We report here that cytoplasmic zinc facilitates the downward regulation of a background Cl- conductance b y an endogenous protein kinase C (PKC) in fish retinal ganglion cell somata and that this regulation is maintained if nanomolar levels of free Zn2+ ar e available. This regulation has not been described previously in any tissu e, as other Cl- currents have been described as reduced by PKC alone, reduc ed by Zn2+ alone, or reduced by both independently. Moreover, control of ca tion currents by a zinc-dependent PKC has not been reported previously. The regulation we have observed thus provides the first electrophysiological m easurements consistent with biochemical measurements of zinc-dependent PKC activity in other systems. These results suggest that contributions of back ground CI conductances to electrical properties of neurons are susceptible to modulation.