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October 7, 1988Science320 citations

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

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KWKenneth B. WalshRKRobert S. Kass

Key Points

  • This research aims to understand how protein kinases A and C regulate potassium and calcium currents in cardiac cells.
  • Utilized cAMP analog 8-CPT cAMP to stimulate protein kinase A in cardiac ventricular myocytes.
  • Measured delayed-rectifier potassium current (IK) and calcium current (ICa) at different temperatures.
  • Activated protein kinase C using phorbol 12,13-dibutyrate and observed its effects on IK and ICa.
  • Stimulation of protein kinase A increased IK by twofold at 32 degrees C, with no effect at 22 degrees C.
  • Protein kinase C also enhanced IK in a temperature-dependent manner, but did not affect ICa.
  • ICa showed consistent increases at both temperatures, independent of protein kinase A activation.

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 (IK) doubled when recorded at 32 degrees C but was not affected at 22 degrees C. In contrast, modulation of the calcium current (ICa) by 8-CPT cAMP was independent of temperature with similar increases in ICa occurring at both temperatures. Stimulation of protein kinase C by phorbol 12,13-dibutyrate also enhanced IK in a temperature-dependent manner but failed to increase ICa 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.

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Cite This Study

Walsh et al. (1988) studied this question.

synapsesocial.com/papers/6a70722d660549caf2c50691https://doi.org/10.1126/science.2845575
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