ELECTRICAL-STIMULATION OF CONTRACTILE ACTIVITY ACCELERATES GROWTH OF CULTURED NEONATAL CARDIOCYTES

An electrical stimulation system was designed to regulate synchronized contractile activity of neonatal rat cardiocytes and to examine the effects of mechanical contraction on cardiocyte growth. Continuous electrical stimulation at a pulse duration of 5 milliseconds and frequency of 3 Hz resulted in a time-dependent accumulation of cell protein that reached 34% above initial values, as measured by the protein-to-DNA ratio. The growth response did not occur using voltage amplitudes that were subthreshold for contraction and was independent of contraction frequencies set at greater than or equal to 0.5 Hz. The RNA-to-DNA ratio increased in parallel to cell protein, indicating that the capacity for protein synthesis was enhanced by contraction. Rates of 28S rRNA synthesis were accelerated twofold in contracting cardiocytes. By comparison, protein and RNA accumulation did not occur in electrically stimulated cardiocytes in which contraction was blocked by either 10 mu mol/L verapamil or by 5 mmol/L 2,3-butanedione monoxime, an inhibitor of actomyosin crossbridge cycling. Electrical stimulation of cardiocyte contraction did not enhance alpha-cardiac actin or myosin heavy chain (alpha+beta) mRNA transcript levels relative to 28S rRNA during the period of rapid growth that occurred over the first 48 hours. It is concluded that (1) electrical stimulation of contraction accelerates cardiocyte growth and RNA accumulation, (2) mechanical contraction is involved in regulating the growth of electrically stimulated cardiocytes, and (3) the levels of cu-actin and myosin heavy chain mRNA increase in proportion to rRNA during the growth of contracting cardiocytes. (Circ Res. 1994;74:448-459.)