The Effect of Thapsigargin on Sarcoplasmic Reticulum Ca2+ Content and Contractions in Single Myocytes of Guinea-pig Heart

Contractures initiated by 1 s superfusion of single myocytes of guinea-pig heart with 10 mM caffeine were used as a relative index of the SR Ca2+ content. Thapsigargin (Tg) in concentration 2 × 10-7M completely blocked Ca2+ uptake during electrical stimulation by the SR from which Ca2+ has been previously depleted by caffeine. Tg did not affect the SR Ca2+ content in the resting myocytes and did not block release of the SR Ca2+ during electrically stimulated contractions (ESCs). It is concluded that in guinea-pig myocytes Tg affects SR Ca2+ by selective blocking the SR Ca2+ uptake. The amplitude of steady state ESCs dropped to 68±5.4% (S.D., n=20) of that of the pre-Tg control. Time to peak contraction increased from 454±82.4 ms to 820±157.4 ms and time of relaxation increased from 368±90.8 ms to 474±87 ms after the SR Ca2+ has been depleted by Tg. Rest decay of contractions, post-extrasystolic potentiation and post-rest potentiation were inhibited.