Activation of ionotropic γ-aminobutyric acid type A (GABAA) receptors depolarizes neurons that have high intracellular [Cl−], causing inhibition or excitation in different cell types. The depolarization often leads to inactivation of voltage-gated Na channels, but additional ionic mechanisms may also be affected. Previously, a simulated model of spider VS-3 mechanosensory neurons suggested that although voltage-activated Na+ current is partially inactivated during GABA-induced depolarization, a slowly activating and inactivating component remains and may contribute to the depolarization. Here, we confirmed experimentally, by blocking Na channels prior to GABA application, that Na+ current contributes to GABA-induced depolarization in VS-3 neurons. Ratiometric Ca2+ imaging experiments combined with intracellular recordings revealed a significant increase in intracellular [Ca2+] when GABAA receptors were activated, synchronous with the depolarization and probably due to Ca2+ influx via low-voltage–activated (LVA) Ca channels. In contrast, GABAB-receptor activation in these neurons was previously shown to inhibit LVA current. Blockade of voltage-gated K channels delayed membrane repolarization, extending GABA-induced depolarization. However, inhibition of Ca channels significantly increased the amplitude of GABA-induced depolarization, indicating that Ca2+-activated K+ current has an even stronger repolarizing effect. Regulation of intracellular [Ca2+] is important for many cellular processes and Ca2+ control of K+ currents may be particularly important for some functions of mechanosensory neurons, such as frequency tuning. These data show that GABAA-receptor activation participates in this regulation.
- Copyright © 2008 by the American Physiological Society