Direct ion channel gating: A new function for intracellular messengers

1. There is widespread belief that intracellular messengers [e.g., Ca²⁺, cyclic AMP, cyclic GMP, inositol-1,4,5-triphosphate (IP3)] assert their actions primarily through activation of protein kinases. 2. In studies of excitable cells protein kinase activation has been shown to alter membrane ionic conductance, presumably through phosphorylation of ion channels (see Levitan, 1985). However, recent reports from several laboratories indicate that intracellular messengers can also affect membrane ionic conductances directly without invoking protein kinase activation. 3. In this article we examine those examples of direct activation of ionic conductances by intracellular messengers which are supported by single-channel studies of isolated membrane patches. The list of cell types displaying this kind of response is growing and includes cells of neuronal as well as nonneuronal origin.