Modification of cardiac sodium current by intracellular application of cAMP.
We examined the effects of intracellular perfusion of cyclic adenosine monophosphate (cAMP) on the sodium current (INa) of guinea-pig ventricular myocytes, using the whole-cell clamp technique. INa was elicited by depolarizing voltage steps (-20 mV) from a variety of holding potentials (-120 to -50 mV), under conditions of 60 mM extracellular Na+ concentration ([Na+]o) and at the temperature of 24-26 degrees C. Intracellular perfusion of cAMP decreased the INa elicited from the holding potentials less negative than -90 mV. In the presence of 1 mM cAMP, for example, the peak INa elicited from -80 mV decreased from 6.0 +/- 2.0 nA to 4.0 +/- 2.2 nA (mean +/- SD, P < 0.02, n = 7) within 3-6 min. In the presence of extracellular 3-isobutyl-1-methylxanthine (IBMX, 20 microM), much lower concentrations of cAMP (0.2 mM) yielded a comparable effect. On the other hand, intracellular perfusion of cAMP increased the INa elicited from very negative holding potentials (< -100 mV). For instance, the application of cAMP (1 mM) increased the INa elicited by step depolarizations from -120 mV (to -20 mV), from 9.9 +/- 2.1 nA to 11.0 +/- 3.1 nA (P < 0.05, n = 5). The former effect was attributed to a marked shift of the steady-state inactivation curve of INa to the negative direction; the voltage of half-inactivation shifted from -77.9 +/- 1.0 to -83.5 +/- 1.4 mV, or by -5.6 mV. The latter effect may be explained by increases in maximum available conductance of INa.(ABSTRACT TRUNCATED AT 250 WORDS)
Muramatsu
H
H
Department of Physiology, Oita Medical University, Japan.
Kiyosue
T
T
Arita
M
M
Ishikawa
T
T
Hidaka
H
H
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D010477:Perfusion; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides
D036341:Intercellular Signaling Peptides and Proteins; D007546:Isoquinolines; D010455:Peptides; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; D015222:Sodium Channels; D013449:Sulfonamides; C085074:Walsh peptide; D012964:Sodium; D000242:Cyclic AMP; D011494:Protein Kinases; D007545:Isoproterenol; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide