Stretch can modify both the electrical activity and intracellular Ca²⁺([Ca²⁺]_i) of cardiac muscle (Calaghan & White, 1999). Because there are Ca²⁺-activated membrane currents in cardiac muscle, these two responses may be linked. We have tested this possibility in single guinea-pig ventricular myocytes.

Guinea-pigs were killed by Schedule 1 methods. Hearts were then removed and single left ventricular cardiac myocytes isolated using a collagenase digestion technique. Carbon fibres were attached to cells and used to stretch them. Microelectrodes containing 600 mM KCl were used to record action potentials. Experiments were performed at a stimulation frequency of 0.5 Hz and a temperature of 36-37 °C. Streptomycin (40 µM) was used to block stretch events. In unstretched cells, 50 µM streptomycin had no effect on myocyte contraction and [Ca²⁺]_i (fura-2) transients (n = 12 cells), or action potentials (n = 6 cells) (P > 0.05, paired t test).

Longitudinal axial stretch, which increased resting sarcomere length (SL) from 1.81 ± 0.01 to 1.97 ± 0.02 µm (mean ± S.E.M.), caused a significant prolongation of action potential duration at 90 % repolarisation (APD₉₀) from 260 ± 14 ms by 16 ± 2 ms (P < 0.05, n = 26 cells, Fig. 1A). In the presence of 40 µM streptomycin this effect of stretch was absent (Fig. 1B). In cells pre-incubated with 5 µM BATPA-AM for 15 min (to buffer [Ca²⁺]_i at a low level), stretch did not prolong APD₉₀ (Fig. 1B).

Our observations are consistent with the hypothesis that a stretch-dependent (streptomycin-sensitive) and Ca²⁺-dependent (BAPTA-sensitive) mechanism or mechanisms combine to modulate the overall electrical response of cardiac myocytes to stretch.

This work was supported by the British Heart Foundation.

Figure 1. A, effect of a stretch ([fullcircle]) that increased sarcomere length from 1.85 to 2.00 µm on the action potential of a guinea-pig ventricular myocyte. B, effect of an 8 ± 0.5 % increase in SL on the change in APD90 in the absence (CON) and presence of 40 µM streptomycin (STREP) and in cells pre-incubated with 5 µM BAPTA-AM (BAPTA). The response in streptomycin- and BAPTA-treated cells was significantly different from untreated cells (P < 0.05, one-way ANOVA).