Effect of gallopamil on cardiac sarcoplasmic reticulum.
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.
Zucchi
R
R
Istituto di Cardiologia, University of Pisa, Italy.
Ronca-Testoni
S
S
Limbruno
U
U
Yu
G
G
Galbani
P
P
Ronca
G
G
Mariani
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D005711:Gallopamil / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism
D012433:Ryanodine; D005711:Gallopamil; D002118:Calcium