Open AccessCytosolic Myocardial Calcium Modulation by ATP-Dependent Potassium Channel Openers and NO Donors
Author(s) -
Monique Laplace,
Tamara Guénoun,
Olivier Montagne,
F. Röser,
Bertrand Crozatier
Publication year - 1999
Publication title -
journal of cardiovascular pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-199903000-00008
Subject(s) - nicorandil , calcium , chemistry , potassium channel , medicine , endocrinology , glibenclamide , cyclic guanosine monophosphate , antagonist , calcium channel , cytosol , atp sensitive potassium channel , biophysics , biochemistry , nitric oxide , receptor , biology , enzyme , diabetes mellitus
The goal of this study was to evaluate, in rat cardiomyocytes, the effects on cytosolic calcium of a pure K-adenosine triphosphate (ATP) channel opener, aprikalim, and those of nicorandil, a dual-acting agent that increases cyclic guanosine monophosphate (cGMP) levels and opens K-ATP channels. These effects were compared with those of a pure NO donor, 3-morpholino-sydnonimine (Sin-1). Ventricular myocytes were isolated from the hearts of adult rats. Changes in cytosolic calcium concentration ([Ca2+]i) were measured by using a Ca2+ indicator, indo-1/AM. Alterations in indo-1 fluorescence were recorded during regular electrical stimulation. After 10 min of pacing, end-diastolic [Ca2+]i was significantly increased as compared with control without significant changes in calcium transient. For doses of 10(-7) to 10(-4) M, aprikalim and nicorandil did not affect significantly the calcium transient. Sin-1 produced a significant decrease in calcium transient (by approximately 20%), which was already maximal at 10(-7) M. When given with the potassium channel antagonist glibenclamide (10(-5) M), nicorandil induced the same effects as those observed with Sin-1. We conclude that potassium channel openers aprikalim and nicorandil do not not decrease calcium transient. Thus the NO-donor properties of nicorandil are not apparent when given alone but appear when ATP-dependent potassium channels are blocked.