FUNCTIONAL EXPRESSION OF LARGE-CONDUCTANCE Ca2+-ACTIVATED POTASSIUM CHANNELS IN LATERAL GLOBUS PALLIDUS NEURONS

The presence of large-conductance Ca2+-activated potassium (BK) channels, which are considered to play an important role in the excitability of neurons, in the highly-excitable lateral globus pallidus (LOP) neurons has yet to be confirmed. In this study, we confirmed the functional expression of BK channels in mouse LOP neurons and investigated the characteristics of their single-channel currents using inside-out patch-clamp recordings. These BK channels had a conductance of 276 pS, were activated by the elevation of both the transmembrane potential and intracellular calcium concentration ([Ca2+](i)), and were completely blocked by the BK channel-specific blocker paxilline (100 nM). In addition, the channel currents were sensitive to high-energy phosphate compounds and low internal pH. The cellular function of these BK channels was then investigated by nystatin-perforated whole-cell recording. Paxilline (100 nM) had no effect on the frequency and half-width of the action potential (AP) in LOP neurons under control conditions, but significantly attenuated the hyperpolarization that was caused by carbonyl cyanide m-chlorophenylhydrazone (CCCP), an inhibitor of ATP synthesis. In addition, the pancreatic beta-cell type ATP-sensitive potassium channel (K-ATP channel) blocker tolbutamide (0.25 mM) also attenuated the hyperpolarization, in a manner similar to paxilline. The voltage-dependent potassium channel blocker tetraethylammonium (TEA, 2 mM) significantly decreased the frequency and increased the half-width of the AP in LOP neurons under control conditions, and attenuated CCCP-induced hyperpolarization to an extent close to that of paxilline. The results presented here suggest that functional BK channels are present in LOP neurons, and may behave as partners of K-ATP channels in the regulation of neuronal activity under metabolic stress conditions. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.