Depolarization of Cardiac Membrane Potential Promotes Calcium Waves

Abstract

A calcium (Ca) wave propagates when Ca sparks recruit new sparks in the adjacent Ca release units (CRUs) in cardiac myocytes. When Ca releases occur, Ca from the sarcoplasmic reticulum (SR) is removed mostly via the SERCA pump and the sodium-calcium exchanger (NCX) from the cytosol. If this removal process is more dominant than the positive feedback process of Ca induced Ca release, Ca waves cannot propagate. The diastolic membrane potential can be hyperpolarized or depolarized by various factors such as hyperkalemia, hypokalemia in the long term or by delayed afterdepolarizations (DADs) in the short term. In this study we investigate how membrane potential affects Ca waves. We use a physiologically detailed ventricular myocyte mathematical model to investigate individual factors which affect Ca wave propagation. We investigate the voltage range of −90 ∼ −70 mV. We find that depolarization of the membrane potential promotes Ca wave propagation and hyperpolarization prevents Ca wave propagation. Ca transport by NCX is determined by membrane potential as well as sodium and Ca concentrations. Depolarized membrane potential reduces NCX-mediated efflux, and thus promotes Ca wave propagation. Moreover, depolarized membrane potential promotes spontaneous Ca releases which can cause initiation of multiple Ca waves. This indicates that during DADs, CRUs interact with not just the immediately adjacent CRUs via Ca diffusions, but also farther CRUs via fast (∼0.1ms) voltage diffusion on the membrane through the NCX. This may also be an additional mechanism of synchronization of Ca waves among multiple cells in tissue.