Mechanism of adenosine-induced inhibition of calcium current in guinea pig ventricular cells.
The mechanism of adenosine-induced inhibition of Ca2+ currents was studied by recording single-channel Ca2+ currents from cell-attached patches on isolated guinea pig ventricular cells with pipettes containing 50 or 100 mM Ba2+. Numerous 100-msec depolarization steps were applied repetitively at 2 Hz from the resting potential of approximately -70 mV. The addition of 0.1 mM adenosine to the superfusate in the presence of 100 nM isoproterenol depressed the isoproterenol-induced increase in ensemble-averaged current: in peak amplitude, from 258 +/- 105% (mean +/- SD) (p less than 0.01) that of control in the presence of isoproterenol to 153 +/- 41% (n = 7) (p less than 0.05) by the addition of adenosine. In these patches, adenosine did not much affect the open probability in nonblank sweeps (control, 0.10 +/- 0.05; isoproterenol, 0.11 +/- 0.08; adenosine and isoproterenol, 0.08 +/- 0.05), but significantly decreased channel availability, defined as the rate of current-containing sweeps in total sweeps (control, 0.36 +/- 0.17; isoproterenol, 0.69 +/- 0.16 [p less than 0.01]; adenosine and isoproterenol, 0.45 +/- 0.20 [p less than 0.01]). The decrease of channel availability by adenosine was due to the shortening of the duration of the available state and the prolongation of that of the unavailable state. The depressive action of adenosine was suppressed by 0.1 mM theophylline. The single-channel conductance in the presence of 100 mM Ba2+ and Bay K 8644 was 26 pS and was not affected by isoproterenol or adenosine. We conclude that adenosine decreases Ca2+ current under beta-adrenergic stimulation mainly by reducing channel availability.
Kato
M
M
Department of Cardiology, Juntendo University School of Medicine, Tokyo, Japan.
Yamaguchi
H
H
Ochi
R
R
D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D013806:Theophylline / Q000494:pharmacology
D015220:Calcium Channels; D013806:Theophylline; D000241:Adenosine; D007545:Isoproterenol; D002118:Calcium