Effects of protein kinase C (PKC) and intracellular calcium ion (Cai2+) on the delayed rectifier K+ current (IK) were investigated in the single ventricular cells of guinea pig by use of an internal-dialysis method and a whole cell voltage-clamp technique. 12-O-tetradecanoylphorbol-13-acetate (TPA, 10(-9) M), an activator of PKC, increased the amplitude of IK in the presence of Cai2+ higher than 10(-10) M. This effect of TPA was mimicked by a synthetic diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG), 50 micrograms/ml, 125 microM, and was blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (10 microM). The above findings suggest that IK channels were phosphorylated by PKC and thereby the amplitude of IK was increased. IK was also increased by elevating the concentration of Cai2+ in the absence of TPA. It is thus indicated that IK channels are modulated by Cai2+ not only through activation of PKC but also directly. Our observation may provide a possible mechanism by which Cai2+ mediates the link between the Ca2+ transients during contraction and the action potential duration.
Protein kinase C enhances the rapidly activating delayed rectifier potassium current,
I
Kr
, through a reduction in C‐type inactivation in guinea‐pig ventricular myocytes