Acidic pH-activated Cl- Current and Intracellular Ca2+ Response in Human Keratinocytes.
10.4196/kjpp.2008.12.4.177
- Author:
Su Jung PARK
1
;
Won Woo CHOI
;
Oh Sang KWON
;
Jin Ho CHUNG
;
Hee Chul EUN
;
Yung E EARM
;
Sung Joon KIM
Author Information
1. Department of Physiology, Seoul National University College of Medicine, Seoul, Korea. sjoonkim@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Keratinocyte;
Extracellular pH;
Anion channel;
Intracellular calcium;
pH-activated Cl- current
- MeSH:
Cell Line;
Estrenes;
Foreskin;
Humans;
Hydrogen-Ion Concentration;
Keratinocytes;
Kinetics;
Membranes;
Pyrrolidinones;
Skin
- From:The Korean Journal of Physiology and Pharmacology
2008;12(4):177-183
- CountryRepublic of Korea
- Language:English
-
Abstract:
The layers of keratinocytes form an acid mantle on the surface of the skin. Herein, we investigated the effects of acidic pH on the membrane current and [Ca2+](c) of human primary keratinocytes from foreskins and human keratinocyte cell line (HaCaT). Acidic extracellular pH (pHe< or =5.5) activated outwardly rectifying Cl- current (I(Cl,pH)) with slow kinetics of voltage-dependent activation. I(Cl,pH) was potently inhibited by an anion channel blocker 4,4`-diisothiocyanostilbene-2,2`-disulphonic acid (DIDS, 73.5% inhibition at 1micrometer). I(Cl,pH) became more sensitive to pHe by raising temperature from 24degrees C to 37degrees C. HaCaT cells also expressed Ca2+ -activated Cl- current (I(Cl,Ca)), and the amplitude of I(Cl,Ca) was increased by relatively weak acidic pHe (7.0 and 6.8). Interestingly, the acidic pHe (5.0) also induced a sharp increase in the intracellular [Ca2+] (delta[Ca2+](acid)) of HaCaT cells. The delta[Ca2+](acid) was independent of extracellular Ca2+, and was abolished by the pretreatment with PLC inhibitor, U73122. In primary human keratinocytes, 5 out of 28 tested cells showed delta[Ca2+](acid). In summary, we found I(Cl,pH) and delta[Ca2+](acid) in human keratinocytes, and these ionic signals might have implication in pathophysiological responses and differentiation of epidermal keratinocytes.
