The Journal of Membrane Biology

, Volume 119, Issue 2, pp 163–170 | Cite as

Na+ channel blockade by cyclic AMP and other 6-aminopurines in neonatal rat heart

  • J. W. Herzig
  • M. Kohlhardt


Elementary Na+ currents were recorded at 19°C in cell attached and inside-out patches from cultured neonatal rat cardiocytes in order to study the effect of cAMP and other 6-aminopurines.

The treatment of the cardiocytes with db-cAMP (1×10−3 mol/liter) led to a decline of reconstructed macroscopic peakINa to 62±7.6% of the initial control value. This reduction in NP0 was mostly accompanied by a decrease in burst activity. Openstate kinetics were preserved even in DPI-modified, noninactivating Na+ channels. Since the stimulator of the adenylate cyclase, forskolin (1×10−6 mol/liter), evoked a similar pattern of response, the NP0 decrease can be considered as the functional correlate of Na+ channel phosphorylation brought about by cAMP-dependent protein kinase. As found in inside-out patches, cAMP (1×10−3 mol/liter) remained effective under cell-free conditions and reduced reconstructed macroscopic peakINA to about 50% of the initial control value when the absence of Mg-ATP at the cytoplasmic membrane surface prevents phosphorylation reactions. A very similar response developed in the cytoplasmic presence of other 6-aminopurines including ATP (1×103 mol/liter), adenosine (1×10−4 mol/liter), adenine (1×10−5 mol/liter) and hypoxanthine (1×10−5 mol/liter). This susceptibility to adenine suggests that cardiac Na+ channelsin situ could sense intracellular fluctuations of adenine nucleotides, most likely of ATP.

Key Words

single cardiac Na+ channels phosphorylation cAMP ATP adenine 


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Copyright information

© Springer-Verlag New York Inc. 1991

Authors and Affiliations

  • J. W. Herzig
    • 1
  • M. Kohlhardt
    • 1
  1. 1.Physiological InstituteUniversity of FreiburgFreiburg/Br.Federal Republic of Germany

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