pISSN 1226-4512 eISSN 2093-3827

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Korean J Physiol Pharmacol 2005; 9(2): 131-134

Published online April 30, 2005

Copyright © The Korean Journal of Physiology & Pharmacology.

Modulation of Large Conductance Ca2⁢-activated K Channel of Skin Fibroblast (CRL-1474) by Cyclic Nucleotides

Jihyun Yun, Seungtae Kim, and Hyoweon Bang

Department of Physiology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea

Abstract

Potassium channels in human skin fibroblast have been studied as a possible site of Alzheimer disease pathogenesis. Fibroblasts in Alzheimer disease show alterations in signal transduction pathway such as changes in Ca2⁢ homeostasis and/or Ca2⁢-activated kinases, phosphatidylinositol cascade, protein kinase C activity, cAMP levels and absence of specific K channel. However, little is known so far about electrophysiological and pharmacological characteristics of large-conductance Ca2⁢-activated K (BKCa) channel in human fibroblast (CRL-1474). In the present study, we found Iberiotoxin- and TEA-sensitive outward rectifying oscillatory current with whole-cell recordings. Single channel analysis showed large conductance K channels (106 pS of chord conductance at ⁢40 mV in physiological K gradient). The 106 pS channels were activated by membrane potential and [Ca2⁢]i, consistent with the known properties of BKCa channels. BKCa channels in CRL-1474 were positively regulated by adenylate cyclase activator (10μM forskolin), 8-Br-cyclic AMP (300μM) or 8-Br-cyclic GMP (300μM). These results suggest that human skin fibroblasts (CR-1474) have typical BKCa channel and this channel could be modulated by c-AMP and c-GMP. The electrophysiological characteristics of fibroblasts might be used as the diagnostic clues for Alzheimer disease.

Keywords: BKCa channel, Fibroblast, Alzheimer disease, Second messenger system, cAMP, cGMP