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Modulation of cardiac sodium channels by cAMP receptors on the myocyte surface

L A Sorbera1, M Morad

  • 1Department of Physiology, University of Pennsylvania, Philadelphia 19104.

Science (New York, N.Y.)
|September 13, 1991
PubMed

Insights

Extracellular cyclic adenosine monophosphate (cAMP) rapidly modulates cardiac sodium channels in various species. This modulation involves a pertussis toxin-sensitive G protein pathway, affecting sodium current and channel availability.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Ion Channel Function

Background:

  • Cardiac sodium channels are crucial for heart electrical activity.
  • Phosphorylation by protein kinase A (PKA) inactivates cardiac sodium channels.
  • The role of extracellular signaling molecules in sodium channel modulation is an area of active research.

Purpose of the Study:

  • To investigate the effect of extracellular cyclic adenosine monophosphate (cAMP) on cardiac sodium channels.
  • To determine the mechanism underlying extracellular cAMP-mediated modulation of sodium channels.

Main Methods:

  • Patch-clamp electrophysiology was used to measure sodium currents in isolated ventricular myocytes from rat, guinea pig, and frog.
  • Experiments involved applying extracellular cAMP and assessing changes in sodium current amplitude and gating properties.
  • Inhibitors such as guanosine-5'-O-(2-thiodiphosphate) and pertussis toxin were used to probe the signaling pathway.

Main Results:

  • Extracellular cAMP rapidly (less than 50 ms), reversibly, and dose-dependently decreased sodium current in ventricular myocytes.
  • This decrease was associated with a 10- to 15-millivolt hyperpolarizing shift in the steady-state availability of the sodium channel.
  • The effects of extracellular cAMP were inhibited by guanosine-5'-O-(2-thiodiphosphate) and pertussis toxin.

Conclusions:

  • Extracellular cAMP modulates cardiac sodium channel function through a rapid, membrane-delimited pathway.
  • The mechanism involves a pertussis toxin-sensitive G protein, distinct from intracellular PKA-mediated phosphorylation.
  • These findings reveal a novel signaling pathway influencing cardiac excitability.

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