Journal
NEUROPHARMACOLOGY
Volume 40, Issue 7, Pages 879-887Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0028-3908(01)00028-4
Keywords
riluzole; 1-ethylbenzimidiazolone; amitriptyline; bicuculline Ca2+-activated K+ channel; 4-aminopyridine
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Small-conductance, calcium-activated K+ channels (SK channels) are voltage-insensitive channels that have been identified molecularly within the last few years. As SK channels play a fundamental role in most excitable cells and participate in afterhyperpolarization (AHP) and spike-frequency adaptation, pharmacological modulation of SK channels may be of significant clinical importance. Here we report the functional expression of SK3 in HEK293 and demonstrate a broad pharmacological profile for these channels. Brain slice studies commonly employ 4-aminopyridine (4-AP) to block voltage-dependent K+ channels or a methyl derivative of bicuculline, a blocker of gamma-aminobutyric acid (GABA)-gated Cl- channels, in order to investigate the role of various synapses in specialized neural networks. However, in this study both 4-AP and bicuculline are shown to inhibit SK3 channeld (IC50 values of 512 muM and 6 muM, respectively) at concentrations lower than those used for brain slice recordings. Riluzole, a potent neuroprotective drug with anti-ischemic, anticonvulsant and sedative effects currently used in the treatment of amyotrophic lateral sclerosis, activates SK3 channels at concentrations of 3 muM and above. Amitriptyline, a tricyclic antidepressive widely used clinically, inhibits SK3 channels with an IC50 of 39.1 +/- 110 CIM (n=6). (C) 2001 Elsevier Science Ltd. All rights reserved.
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