Modulation of Kv4 channels, key components of rat ventricular transient outward K1 current, by PKC

ventricular transient outward K1 current, by PKC. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H1775–H1786, 1997.— Current evidence suggests that members of the Kv4 subfam-ily may encode native cardiac transient outward current (Ito). Antisense hybrid-arrest with oligonucleotides targeted to Kv4 mRNAs specifically inhibited rat ventricular Ito, support-ing this hypothesis. To determine whether protein kinase C (PKC) affects Ito by an action on these molecular components, we compared the effects of PKC activation on Kv4.2 and Kv4.3 currents expressed in Xenopus oocytes and rat ventricu-lar Ito. Phorbol 12-myristate 13-acetate (PMA) suppressed both Kv4.2 and Kv4.3 currents as well as native Ito, but not after preincubation with PKC inhibitors (e.g., chelerythrine). An inactive stereoisomer of PMA had no effect. Phenylephrine or carbachol inhibited Kv4 currents only when coexpressed