Activity-Independent Homeostasis in Rhythmically Active Neurons

Abstract

The shal gene encodes the transient potassium current (I_A) in neurons of the lobster stomatogastric ganglion. Overexpression of Shal by RNA injection into neurons produces a large increase in I_A, but surprisingly little change in the neuron's firing properties. Accompanying the increase in I_A is a dramatic and linearly correlated increase in the hyperpolarization-activated inward current (I_h). The enhanced I_h electrophysiologically compensates for the enhanced I_A, since pharmacological blockade of I_h uncovers the physiological effects of the increased I_A. Expression of a nonfunctional mutant Shal also induces a large increase in I_h, demonstrating a novel activity-independent coupling between the Shal protein and I_h enhancement. Since I_A and I_h influence neuronal activity in opposite directions, our results suggest a selective coregulation of these channels as a mechanism for constraining cell activity within appropriate physiological parameters.