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Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes
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Isolation and Kv Channel Recordings in Murine Atrial and Ventricular Cardiomyocytes

Published on: March 12, 2013

Independent and exclusive modulation of cardiac delayed rectifying K+ current by protein kinase C and protein kinase

C F Lo1, R Numann

  • 1Wyeth-Ayerst Research, Princeton, NJ, USA.

Circulation Research
|November 14, 1998
PubMed

Insights

Protein kinase C (PKC) and protein kinase A (PKA) differentially regulate the cardiac slow delayed rectifying K+ (IKs) current. These kinases modulate IKs current in a mutually exclusive manner, suggesting complex phosphorylation site interactions within the minK-KvLQT1 channel.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Electrophysiology

Background:

  • The cardiac slow delayed rectifying K+ (IKs) current is crucial for shaping the cardiac action potential.
  • While human and cat minK cDNA are known, their regulation by protein kinases remains uncharacterized.
  • Understanding IKs current modulation is vital for cardiac electrophysiology research.

Purpose of the Study:

  • To characterize the complex modulation of human and cat IKs currents by protein kinase C (PKC) and protein kinase A (PKA).
  • To investigate the interaction and potential mutual exclusivity between PKC and PKA in regulating IKs current.

Main Methods:

  • Expression of minK in Xenopus oocytes to study IKs current.
  • Activation of PKC using phorbol ester (PDD) and diacylglycerol analogues.
  • Activation of PKA to assess its effect on IKs current.
  • Investigating the effects of pre-modulation by PKC on PKA activity and vice versa.

Main Results:

  • PKC activation by PDD causes a biphasic effect: initial increase followed by a decrease in IKs current.
  • PKA activation leads to a sustained increase in IKs current.
  • PKC and PKA modulate IKs current in a mutually exclusive manner; pre-modulation by one prevents the effect of the other.
  • PKC exhibits dose- and duration-dependent effects, suggesting at least two independent phosphorylation sites on the minK-KvLQT1 channel.

Conclusions:

  • PKC and PKA exert complex, mutually exclusive regulation over the cardiac IKs current.
  • Multiple interacting phosphorylation sites on the minK-KvLQT1 channel are involved in kinase-mediated modulation.
  • These findings provide critical insights into the intricate mechanisms governing cardiac action potential duration.

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