Extrinsic factors influence the expression of voltage-gated K currents on neonatal rat sympathetic neurons

Abstract

Voltage-gated potassium (K) currents are important in controlling a neuron's excitability. We have shown previously (McFarlane and Cooper, 1992) that neonatal superior cervical ganglia (SCG) neurons express three voltage- gated K currents: a noninactivating delayed-rectifier type current (I(K)), a rapidly inactivating A-current (I(Af)), and a slowly inactivating A-current (I(As)). When grown in culture for 4 weeks without other cell types, SCG neurons lose their expression of I(Af) and I(As), suggesting that an extrinsic factor(s) is involved in controlling the expression of these currents. In vivo, SCG neurons are surrounded by non-neuronal cells. Therefore, in this study we investigated whether the ganglionic non-neuronal cells provide a factor required for A-current expression. We show that postnatal day 1 (P1) SCG neurons continue to express I(Af) and I(As) when cocultured with their ganglionic non-neuronal cells. Medium conditioned by ganglionic non-neuronal cells mimics the non-neuronal cell influence on I(Af) and I(As) expression, suggesting that the effects of non-neuronal cells are mediated by way of a secreted factor. Ciliary neurotrophic factor, a factor present in peripheral non-neuronal cells, has similar effects to those of ganglionic cell-conditioned medium. Moreover, we find that the dependence of I(Af) on a non-neuronal cell factor is developmentally regulated; P14 neurons grown in culture without other cell types continue to express I(Af). However, I(As) on P14 neurons maintains its dependence on a factor from non-neuronal cells. Finally, in addition to extrinsic control of voltage-gated K currents, we suggest that SCG neurons use intrinsic mechanisms to coordinate their expression of I(Af), I(As), and I(K) such that changes in one K current are compensated for by reciprocal changes in one or more of the other K currents.