Modulation of Large Conductance Ca2+-activated K+ Channel of Skin Fibroblast (CRL-1474) by Cyclic Nucleotides.
- Author:
Jihyun YUN
1
;
Seungtae KIM
;
Hyoweon BANG
Author Information
1. Department of Physiology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea. haena@cau.ac.kr
- Publication Type:Original Article
- Keywords:
BKCa channel;
Fibroblast;
Alzheimer disease;
Second messenger system;
cAMP;
cGMP
- MeSH:
Adenylyl Cyclases;
Alzheimer Disease;
Fibroblasts*;
Homeostasis;
Humans;
Membrane Potentials;
Nucleotides, Cyclic*;
Patch-Clamp Techniques;
Phosphatidylinositols;
Phosphotransferases;
Potassium Channels;
Protein Kinase C;
Second Messenger Systems;
Signal Transduction;
Skin*
- From:The Korean Journal of Physiology and Pharmacology
2005;9(2):131-135
- CountryRepublic of Korea
- Language:English
-
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 (10microM forskolin), 8-Br-cyclic AMP (300microM) or 8-Br-cyclic GMP (300microM). 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.
