Effects of caffeine, verapamil, lithium, and KB-R7943 on mechanics and energetics of rat myocardial bigeminies

Abstract

We examined the effects of pharmacological alteration of Ca2+ sources on mechanical and energetic properties of paired-pulse ("bigeminic") contractions. The fraction of heat release that is related to pressure development and pressure-independent heat release were measured during isovolumic contractions in arterially perfused rat ventricles. The heat released by regular and bigeminic contractions showed two brief pressure-independent components (H1 and H2) and a pressure-dependent component (H3). We used the ratio of active heat (Ha') to pressure-time integral (PtI) and the ratio of H3 to PtI to estimate the energetic cost of muscle contraction (overall economy) and pressure maintenance (contractile economy), respectively. Neither of these ratios was affected by stimulation pattern. Caffeine (an inhibitor of sarcoplasmic reticulum function) significantly decreased mechanical responses and increased the energetic cost of contraction (delta = 101 +/- 12.6%). Verapamil (an L-type Ca2+ channel blocker) decreased pressure maintenance of extrasystolic (delta = 43.4 +/- 3.7%) and postextrasystolic (delta = 37.5 +/- 3.5%) contractions without affecting postextrasystolic potentiation, suggesting that a verapamil-insensitive fraction is responsible for potentiation. The verapamil-insensitive fraction was further studied in the presence of lithium (45 mM) and KB-R7943 (5 microM), inhibitors of the Na+/Ca2+ exchanger. Both agents decreased all mechanical responses, including postextrasystolic potentiation (delta = 67.3 +/- 3.3%), without altering overall or contractile economies, suggesting an association of the verapamil-insensitive Ca2+ fraction to the sarcolemmal Na+/Ca2+ exchanger. The effect of the inhibitors of the Na+/Ca2+ exchanger on potentiation suggests an increased participation of extracellular Ca2+ (and, thus, a redistribution of the relative participation of the Ca2+ pools) during bigeminic contractions in rat myocardium.

Physical manipulation of calcium oscillations facilitates osteodifferentiation of human mesenchymal stem cells

“…Note that treatment of hMSCs with Li 3+ blocked the [Ca 2+ ] i oscillations (34). Since Li 3+ is known to inhibit the SACCs (35), it appears plausible that SACCs mediate the Ca 2+ influx required to sustain the [Ca 2+ ] i oscillations in the undifferentiated hMSCs. The electrocoupling mechanisms mediating changes in the [Ca 2 +] i could depend on the strength of simulation and the cell type, however.…”

Muscle heat: a window into the thermodynamics of a molecular machine

“…The technique immediately produced a flurry of publications (18, 114 -116, 120). It was later extended to accommodate the perfused rat whole heart, as well as either its isolated left ventricle or right atrium (125), complete with indwelling left ventricular balloon to alter mechanical energy demand (17,26,103,104,125) and, subsequently, the mouse heart (118), culminating in a demonstration of measuring the heat production of aliquots of isolated cardiac myocytes (117). Interestingly, the technique has not been adopted by other groups in the interim.…”

Changes in the Rhythmoinotropic Dependence of the Myocardium in Rats with Postinfarction Cardiosclerosis after β1-Adrenoreceptor Blocking

“…After an extrasystolic exposure 0.225 sec after the cycle beginning the PEC amplitude increased by 51% (p<0.01) vs. the regular contraction, while after an extra electrical pulse 0.25 sec after the cycle beginning it was 156% of the regular cycle values (p<0.01). This inotropic reaction is explained by the fact that an extra electrical pulse initiates additional entry of external calcium ions into cardiomyocyte myo- plasm; these ions accumulate in the SR and participate in PEC [11,13].…”