Contributions of voltage- and Ca2+-activated conductances to GABA-induced depolarization in spider mechanosensory neurons.
Activation of ionotropic gamma-aminobutyric acid type A (GABA(A)) 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(2+) imaging experiments combined with intracellular recordings revealed a significant increase in intracellular [Ca(2+)] when GABA(A) receptors were activated, synchronous with the depolarization and probably due to Ca(2+) influx via low-voltage-activated (LVA) Ca channels. In contrast, GABA(B)-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 Ca(2+)-activated K(+) current has an even stronger repolarizing effect. Regulation of intracellular [Ca(2+)] is important for many cellular processes and Ca(2+) control of K(+) currents may be particularly important for some functions of mechanosensory neurons, such as frequency tuning. These data show that GABA(A)-receptor activation participates in this regulation.
Panek
Izabela
I
Department of Physiology and Biophysics, Dalhousie University, Halifax, NS, Canada.
Höger
Ulli
U
French
Andrew S
AS
Torkkeli
Päivi H
PH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects*; D020748:Mibefradil / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D013112:Spiders / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015222:Sodium Channels; D009118:Muscimol; D020748:Mibefradil; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D002118:Calcium