Keratinocyte K+ channels mediate Ca2+-induced differentiation.
K+ channel activation has been associated with growth or differentiation in many cells. We have previously identified a 70-pS K+ channel that was found only in differentiated involucrin-positive cells. In this study we examined the role of K+ channels in Ca2+-induced keratinocyte differentiation. Consistent with our previous report, we found that a K+ conductance developed only in cells cultured in high extracellular Ca2+. Addition of charybdotoxin or verapamil blocked these K+ channels and inhibited Ca2+-induced differentiation, as assessed by cornified envelope formation or transglutaminase activity. These results suggest that K+ channel activation is necessary for Ca2+-induced differentiation. Finally, we used (125)I-labeled charybdotoxin to demonstrate the presence of K+ channels in intact human and mouse epidermis, hair follicles, and eccrine glands, indicating that these channels are found in keratinocytes both in vitro and in vivo. Thus K+ channels may moderate Ca2+ influx in more differentiated keratinocytes and may play a central role in keratinocyte differentiation.
Mauro
T
T
Department of Dermatology, University of CA, San Francisco, California, USA.
Dixon
D B
DB
Komuves
L
L
Hanley
K
K
Pappone
P A
PA
D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D004439:Eccrine Glands / Q000737:chemistry; D004817:Epidermis / Q000737:chemistry; D018859:Hair Follicle / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn; D007457:Iodine Radioisotopes; D015603:Keratinocytes / Q000737:chemistry* / Q000166:cytology*; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000032:analysis* / Q000502:physiology*; D012604:Scorpion Venoms / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D007457:Iodine Radioisotopes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012604:Scorpion Venoms; D018999:Charybdotoxin; D014700:Verapamil; D011188:Potassium; D002118:Calcium