Activation of protein kinase C by PMA suppressed Kv4.2 and Kv4.3 currents and native rat ventricular transient outward K+ current, an effect prevented by PKC inhibitors.
PKC activation suppresses Kv4.2 and Kv4.3 channels, which are key components of the rat ventricular transient outward potassium current.
Current evidence suggests that members of the Kv4 subfamily may encode native cardiac transient outward current (I(to)). Antisense hybrid-arrest with oligonucleotides targeted to Kv4 mRNAs specifically inhibited rat ventricular I(to), supporting this hypothesis. To determine whether protein kinase C (PKC) affects I(to) 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 ventricular I(to). Phorbol 12-myristate 13-acetate (PMA) suppressed both Kv4.2 and Kv4.3 currents as well as native I(to), 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, respectively, with alpha1C-adrenergic or M1 muscarinic receptors (this inhibition was also prevented by chelerythrine). The voltage dependence and inactivation kinetics of Kv4.2 were unchanged by PKC, but small effects on the rates of inactivation and recovery from inactivation of native I(to) were observed. Thus Kv4.2 and Kv4.3 proteins are important subunits of native rat ventricular I(to), and PKC appears to reduce this current by affecting the molecular components of the channels mediating I(to).
Nakamura et al. (Wed,) reported a other. PKC activation (PMA, phenylephrine, carbachol) vs. PKC inhibitors (chelerythrine) or inactive stereoisomer was evaluated on Kv4.2, Kv4.3, and native I(to) currents. Activation of protein kinase C by PMA suppressed Kv4.2 and Kv4.3 currents and native rat ventricular transient outward K+ current, an effect prevented by PKC inhibitors.