Premium
Effects of verapamil on ischaemia‐induced impairment of ATP‐dependent calcium extrusion in rat heart sarcolemma
Author(s) -
Amsterdam F. Th. M.,
Goddijn M.M.,
Haas M.,
Punt N.C.,
Zaagsma J.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb16877.x
Subject(s) - sarcolemma , verapamil , calcium , perfusion , ischemia , vesicle , chemistry , medicine , diltiazem , pharmacology , endocrinology , biochemistry , biology , membrane
1 The effects of ischaemia and reperfusion were studied on adenosine 5′‐triphosphate (ATP)‐dependent 45 Ca 2+ ‐transport in rat heart sarcolemma vesicles. 2 The effect of verapamil, 1 μmoll −1 , was studied by pretreatment of the hearts during Langendorff‐perfusion and in vitro by adding the drug after isolation of the vesicles. 3 Without drug pretreatment the Ca 2+ ‐uptake appeared to be strongly reduced after 30 and after 60 min of global ischaemia, whereas after 30 min of reperfusion it was restored to slightly above the control level. 4 Verapamil pretreatment during the Langendorff perfusion significantly increased Ca 2+ ‐uptake in sarcolemma vesicles both before the onset of ischaemia and after 30 min of reperfusion, whereas no beneficial effect was found on the impaired uptake activity during the ischaemic period. 5 When tested in vitro after the isolation of the sarcolemma vesicles, verapamil only inhibited the Ca 2+ ‐uptake activity with an IC 50 of 112 μmol l −1 , which was increased to 250μmol l −1 after ischaemia and reperfusion. 6 The present study indicates that pretreatment with verapamil, 1 μmol l −1 , of the intact rat heart activates an ATP‐dependent Ca 2+ extrusion process that may contribute to decrease cellular calcium levels in control and, more importantly, in a reperfusion situation. In contrast, in vitro only a less potent inhibition of the extrusion process was found, indicating that physiological regulatory mechanisms may be altered in the vesicles.