K+ channel activation has been associated with growth or differentiati
on in many cells. We have previously identified a 70-pS K+ channel tha
t 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+ channel
s and inhibited Ca2+-induced differentiation, as assessed by cornified
envelope formation or transglutaminase activity. These results sugges
t that K+ channel activation is necessary for Ca2+-induced differentia
tion. Finally, we used I-125-labeled charybdotoxin to demonstrate the
presence of K+ channels in intact human and mouse epidermis, hair foll
icles, and eccrine glands, indicating that these channels are found in
keratinocytes both in vitro and in vivo. Thus K+ channels may moderat
e Ca2+ influx in more differentiated keratinocytes and may play a cent
ral role in keratinocyte differentiation.