Contributions of Voltage- and Ca -Activated Conductances to GABA-Induced Depolarization in Spider Mechanosensory Neurons

Panek I, Höger U, French AS, Torkkeli PH. Contributions of voltageand Ca -activated conductances to GABA-induced depolarization in spider mechanosensory neurons. J Neurophysiol 99: 1596–1606, 2008. First published January 23, 2008; doi:10.1152/jn.01267.2007. Activation of ionotropic -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 Ca imaging experiments combined with intracellular recordings revealed a significant increase in intracellular [Ca ] when GABAA receptors were activated, synchronous with the depolarization and probably due to Ca 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 GABAinduced depolarization, indicating that Ca -activated K current has an even stronger repolarizing effect. Regulation of intracellular [Ca ] is important for many cellular processes and Ca 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.