Beta-adrenergic inhibition of cardiac sodium channels by dual G-protein pathways.
The signaling pathways by which beta-adrenergic agonists modulate voltage-dependent cardiac sodium currents are unknown, although it is likely that adenosine 3'5'-monophosphate (cAMP) is involved. Single-channel and whole-cell sodium currents were measured in cardiac myocytes and the signal transducing G protein Gs was found to couple beta-adrenergic receptors to sodium channels by both cytoplasmic (indirect) and membrane-delimited (direct) pathways. Hence, Gs can act on at least three effectors in the heart: sodium channels, calcium channels, and adenylyl cyclase. The effect on sodium currents was inhibitory and was enhanced by membrane depolarization. During myocardial ischemia the sodium currents of depolarized cells may be further inhibited by the accompanying increase in catecholamine levels.
Schubert
B
B
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030.
VanDongen
A M
AM
Kirsch
G E
GE
Brown
A M
AM
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction; D015222:Sodium Channels / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology
D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D015222:Sodium Channels; D013873:Thionucleotides; D015124:8-Bromo Cyclic Adenosine Monophosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D007545:Isoproterenol