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Expression and biological significance of Ca²⁺-activated ion channels in human keratinocytes

Department of Physiology, University of Munich, D-80336 Munich, Germany

¹Correspondence: Department of Physiology, University of Munich, Pettenkoferstr. 12, D-80336 Munich, Germany. E-mail: c.alzheimer{at}lrz.uni-muenchen.de

In whole-cell recordings from HaCaT keratinocytes, ATP, bradykinin, and histamine caused a biphasic change of the membrane potential consisting of an initial transient depolarization, followed by a pronounced and long-lasting hyperpolarization. Flash photolysis of caged IP₃ mimicked the agonist-induced voltage response, suggesting that intracellular Ca²⁺ release and subsequent opening of Ca²⁺-activated ion channels serve as the common transduction mechanism. In contrast, cAMP- and PKC-dependent pathways were not involved in the electrophysiological effects of the extracellular signaling molecules. The depolarization was predominantly mediated by a DIDS- and niflumic acid-sensitive Cl^- current, whereas a charybdotoxin- and clotrimazole-sensitive K⁺ current underlay the prominent hyperpolarization. Consistent with the electrophysiological data, RT-PCR showed that HaCaT keratinocytes express two types of Ca²⁺-activated Cl^- channels, CaCC2 and CaCC3 (CLCA2), as well as the Ca²⁺-activated K⁺ channel hSK4. That the pronounced hSK4-mediated hyperpolarization bears significance on the growth and differentiation properties of keratinocytes is suggested by RNase protection assays showing that hSK4 mRNA expression is strongly down-regulated under conditions that allow keratinocyte differentiation. hSK4 might thus play a role in linking changes in membrane potential to the biological fate of keratinocytes.—Koegel, H., Alzheimer, C. Expression and biological significance of Ca²⁺-activated ion channels in human keratinocytes.

Key Words: ATP-evoked change of membrane potential • P2Y2 receptor and intracellular Ca²⁺ release • Ca²⁺-activated Cl^- channels • hSK4 • proliferation and differentiation of keratinocytes

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