The effect of acidosis on systolic Ca2+ and sarcoplasmic reticulum calciumcontent in isolated rat ventricular myocytes

1.We have investigated the mechanisms responsible for the changes of systol ic Ca2+ that occur in voltage-clamped rat ventricular myocytes during acido sis produced by application of the weak acid butyrate (30 mM). Intracellula r pH regulation was inhibited with dimethylamiloride (bicarbonate-free solu tion). 2. The application of butyrate produced an intracellular acidification of 0 .33 pH units. This was accompanied by a decrease in systolic Ca2+ to about 50 % of control. However, within 2 min, systolic Ca2+ returned to control l evels. 3. The decrease in systoIic Ca2+ was accompanied by a decrease in the Na+-C a2+ exchange current observed on repolarisation so that the calculated Ca2 efflux on Na+-Ca2+ exchange was less than the entry on the L-type Ca2+ cur rent. The magnitude of the Na+-Ca2+ er;change current recovered along with systolic Ca2+ until it equalled the Ca2+ entry on the L-type Ca2+ current. 4. From the measurement of Ca2+ fluxes, it was calculated that, during acid osis, the cell gains 121.6 +/- 16.2 mu mol l(-1) of Ca2+. This is equal to the measured increase of sarcoplasmic reticulum (SR) calcium content obtain ed by applying caffeine (20 mM) and integrating the resulting Na+-Ca2+ exch ange current. 5. We conclude that the recovery of the amplitude of the systolic Ca2+ tran sient is due to decreased SR calcium release, resulting in reduced Ca2+ eff lux from the cell leading to increased SR calcium content.