Arginine vasopressin-induced potentiation of unitary L-type Ca2+ channel current in guinea pig ventricular myocytes.
The effects of arginine vasopressin (AVP) on L-type Ca2+ channels were studied by recording single-channel activity from cell-attached patches on isolated guinea pig ventricular myocytes, with 100 mmol/L Ba2+ used as the charge carrier. Bath application of AVP (100 nmol/L) reversibly increased channel open probability by a factor of 2.92 +/- 1.43 (n = 15) because of the increased number of channel openings and increased open times. AVP did not change the amplitudes of single-channel currents (1.17 +/- 0.10 pA in the control condition and 1.12 +/- 0.11 pA after AVP, at +20 mV; n = 6). In our experimental conditions, in which myocytes were bathed in Ca(2+)-free high-potassium solutions, AVP-induced potentiation was observed without changes in [Ca2+]i measured by fura 2 fluorescence signals (estimated [Ca2+]i, approximately 80 nmol/L). The AVP-induced increase in channel open probability was abolished by OPC-21268 (8 mumol/L), a specific blocker of V1 receptor, but not by a V2 blocker, OPC-31260 (5 mumol/L). AVP-induced potentiation was also suppressed by a broad-spectrum protein kinase inhibitor, H7 (100 mumol/L, bath application), but not by H89 (1 mumol/L), a blocker with high specificity to protein kinase A. AVP application after the treatment by phorbol ester (phorbol 12-myristate 13-acetate, 100 nmol/L for 1 hour) failed to potentiate the channel activity. These results raised the possibility that protein kinase C might be involved during signal transduction. Our results provide direct evidence that AVP potentiates cardiac L-type Ca2+ currents via V1 receptor stimulation.
Zhang
S
S
Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
Hirano
Y
Y
Hiraoka
M
M
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D005470:Fluorometry; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007700:Kinetics; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D017483:Receptors, Vasopressin / Q000187:drug effects
D015220:Calcium Channels; D010703:Phorbol Esters; D047428:Protein Kinase Inhibitors; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D002118:Calcium