CLONING AND EXPRESSION OF A K(V)1.2 CLASS DELAYED RECTIFIER K-MUSCLE(CHANNEL FROM CANINE COLONIC SMOOTH)

A cDNA (CSMK1) encoding a delayed rectifier K+ channel of the K(v)1.2 class was cloned from canine colonic circular smooth muscle and expres sed in Xenopus oocytes. These channels appear to be uniquely expressed in gastrointestinal muscles and may participate in the electrical slo w wave activity. Functional expression of CSMK1 in Xenopus oocytes dem onstrated a K+ current that activated in a voltage-dependent manner up on depolarization. This current was highly sensitive to 4-aminopyridin e (IC50, 74 muM). A low-conductance K+ channel was identified in insid e-out patches from oocytes injected with CSMK1. This channel displayed a linear current-voltage relation with a slope conductance of 14 pS. The channels were blocked in a concentration-dependent manner by 4-ami nopyridine. Northern blot analysis demonstrated that CSMK1 is expresse d in a wide variety of gastrointestinal smooth muscles. Portal vein, r enal artery, and uterus do not express CSMK1, suggesting that, among s mooth muscles, expression of this K+ channel may be restricted to gast rointestinal smooth muscles. CSMK1 is 91% homologous to RAK, a delayed rectifier K+ channel cloned from rat heart, but displays unique pharm acological properties and tissue distribution.