Regulation of a Heart Potassium Channel by Protein Kinase A and C

Abstract
The enzymes adenosine 3′,5′-monophosphate (cAMP)-dependent protein kinase (protein kinase A) and protein kinase C regulate the activity of a diverse group of cellular proteins including membrane ion channel proteins. When protein kinase A was stimulated in cardiac ventricular myocytes with the membrane-soluble cAMP analog 8-chlorphenylthio cAMP (8-CPT cAMP), the amplitude of the delayed-rectifier potassium current ( I K ) doubled when recorded at 32°C but was not affected at 22°C. In contrast, modulation of the calcium current ( I Ca ) by 8-CPT cAMP was independent of temperature with similar increases in I Ca occurring at both temperatures. Stimulation of protein kinase C by phorbol 12,13-dibutyrate also enhanced I K in a temperature-dependent manner but failed to increase I Ca at either temperature. Thus, cardiac delayed-rectifier potassium but not calcium channels are regulated by two distinct protein kinases in a similar temperature-dependent fashion.