Inhibition of contractile activity with verapamil accelerated myosin heavy chain degradation, whereas BDM did not, indicating MHC half-life follows changes in intracellular calcium.
Intracellular calcium transients, rather than mechanical contractile activity, appear critical in maintaining myofibrillar assembly and preventing accelerated myosin heavy chain proteolysis in neonatal rat ventricular myocytes.
Blockade of L-type Ca2+ channels in spontaneously contracting cultured neonatal rat ventricular myocytes causes contractile arrest, myofibrillar disassembly, and accelerated myofibrillar protein turnover. To determine whether myofibrillar protein turnover. To determine whether myofibrillar atrophy results indirectly from loss of mechanical signals or directly from alterations in intracellular Ca2+ concentration (Ca2+i), contractile activity was inhibited with verapamil (10 microM) or 2,3-butanedione monoxime (BDM), and their effects on cell shortening, Ca2+i, and myosin heavy chain (MHC) turnover were assessed. Control cells demonstrated spontaneous Ca2+i transients (peak amplitude 232 +/- 15 nM, 1-2 Hz) and vigorous contractile activity. Verapamil inhibited shortening by eliminating spontaneous Ca2+i transients. Low concentrations of BDM (5.0-7.5 mM) had no effect on basal or peak Ca2+i transient amplitude but reduced cell shortening, whereas 10 mM BDM reduced both Ca2+i transient amplitude and shortening. Both agents inhibited MHC synthesis, but only verapamil accelerated MHC degradation. Thus MHC half-life does not change in parallel with contractile activity but rather more closely follows changes in Ca2+i. Ca2+i transients appear critical in maintaining myofibrillar assembly and preventing accelerated MHC proteolysis.
Byron et al. (Fri,) conducted a other in Cultured neonatal rat ventricular myocytes. Verapamil or 2,3-butanedione monoxime (BDM) vs. Control cells was evaluated on Cell shortening, [Ca2+]i, and myosin heavy chain (MHC) turnover. Inhibition of contractile activity with verapamil accelerated myosin heavy chain degradation, whereas BDM did not, indicating MHC half-life follows changes in intracellular calcium.
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