Acidic pH-activated Cl- current and intracellular Ca2+ response in human keratinocytes

作者：Park Su Jung; Choi Won Woo; Kwon Oh Sang; Chung Jin Ho; Eun Hee Chul; Earm Yung E; Kim Sung Joon^*

来源：Korean Journal of Physiology and Pharmacology, 2008, 12(4): 177-183.

• keratinocyte
• extracellular pH
• anion channel
• intracellular calcium
• pH-activated Cl- current

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+] of human primary keratinocytes from foreskins and human keratinocyte cell line (HaCaT). Acidic extracellular pH (pH(c)<= 5.5) activated outwardly rectifying Cl- current (I-Cl,I-pH) with slow kinetics of voltage-dependent activation. I-Cl,I-pH was potently inhibited by an anion channel blocker 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS, 73.5% inhibition at 1 mu M). I-Cl,I-pH became more sensitive to pH(e) by raising temperature from 24 degrees C to 37 degrees C. HaCaT cells also expressed Ca2+-activated Cl- current (I-Cl,I-Ca), and the amplitude of I-Cl,I-Ca was increased by relatively weak acidic pH, (7.0 and 6.8). Interestingly, the acidic pH(e) (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 A [Ca2+](acid). In summary, we found I-Cl,I-pH and Delta[Ca2+](acid) in human keratinocytes, and these ionic signals might have implication in pathophysiological responses and differentiation of epidermal keratinocytes.

• 出版日期2008-8