Alterations in action potential profile enhance excitation-contraction coupling in rat cardiac myocytes

1. Action potential (AP) prolongation typically occurs in heart disease due to reductions in transient outward potassium currents (I-omega), and is as sociated with increased Ca2+ transients. We investigated the underlying mec hanisms responsible for enhanced Ca2+ transients in normal isolated rat ven tricular myocytes in response to the AP changes that occur following myocar dial infarction. 2. Normal myocytes stimulated with a train of long post-myocardial infarcti on (MI) APs showed a 2.2-fold elevation of the peak Ca2+ transient and a 2. 7-fold augmentation of fractional cell shortening, relative to myocytes sti mulated with a short control AP. 3. The steady-state Ca2+ load of the sarcoplasmic reticulum (SR) was increa sed 2.0-fold when myocytes were stimulated with trains of long post-MI APs (111 +/- 21.6 mu mol l(-1)) compared with short control APs (56 +/- 7.2 mu mol l(-1)). 4. Under conditions of equal SR Ca2+ load, long post-MI APs still resulted in a 1.7-fold increase in peak [Ca2+](i) and a 3.8-fold increase in fractio nal cell shortening relative to short control APs, establishing that change s in the triggering of SR Ca2+ release are largely responsible for elevated Ca2+ transients following AP prolongation. 5. Fractional SR Ca2+ release calculated from the measured SR Ca2+ load and the integrated SR Ca2+ fluxes was 24 +/- 3 and 111 +/- 2 % following post- MI and control APs, respectively. 6. The fractional release (FR) of Ca2+ from the SR divided by the integrate d L-type Ca2+ flux (FR/integralF(Ca,L)) was increased 1.2-fold by post-MI A Ps compared with control APs. Similar increases in excitation-contraction ( E-C) coupling gains were observed establishing enhanced E-C coupling effici ency. 7. Our findings demonstrate that AP prolongation alone can markedly enhance E-C coupling in normal myocytes through increases in the L-type Ca2+ curre nt (I-CaL) trigger combined with modest enhancements in Ca2+ release effici ency. We propose that such changes in AP profile in diseased myocardium may contribute significantly to alterations in E-C coupling independent of oth er biochemical or genetic changes.