We investigated the effect of
gallopamil on cardiac sarcoplasmic reticulum (SR) function. Heavy SR was prepared from bovine ventricular muscle.
Oxalate-supported
calcium uptake was stimulated by
gallopamil at concentrations ranging from 10 to 300 nM, whereas higher concentrations were ineffective. Peak stimulation averaged 25-30% of control
calcium uptake and was observed at free
calcium concentrations ranging from 1 to 6 microM.
Calcium uptake is actually the difference between active
calcium transport by SR
calcium-
adenosine triphosphate (
calcium-ATPase), and passive efflux through SR
calcium-release channels. In the presence of 300 microM of
ryanodine, a blocker of SR channels,
calcium uptake increased by 43% under control conditions, but not further stimulation was produced by
gallopamil. SR
calcium-ATPase was not affected by
gallopamil. Similar results were obtained when
oxalate-supported
calcium uptake was determined with use of unfractionated homogenate obtained from rat hearts. We conclude that
gallopamil acts on SR
calcium-release channels and reduces the probability of channel opening and/or channel conductivity. The dose-response curve is bell shaped, and the maximum effect, which corresponds to 65% of the maximum effect of
ryanodine, is achieved at therapeutic concentrations. Such action might contribute to the beneficial effect of
gallopamil in the treatment of
myocardial ischemia.