Postnatal Development of Calcium Signaling in Rat Cardiomyocytes

Abstract

During development, cardiac myocytes undergo rapid growth and structural remodeling. With increased cell size and increased requirements for calcium for contraction, excitation-contraction coupling becomes increasingly dependent on calcium-induced calcium release (CICR). Extending into the interior of the cell, t-tubules form a network securing signal transduction into the whole volume of the cell.We studied the development of L-type calcium currents and of t-tubules in ventricular myocytes of neonatal and young rats (ages 2-18 and 28 days). Calcium currents were recorded in isolated ventricular myocytes (80 ms depolarization from −50 to 0 mV) using patch-clamp. Plasma membrane-specific fluorescent probe FM 4-64 was used to observe formation of t-tubules in myocytes using isolated cells and intact myocardial tissue by laser-scanning confocal microscopy.Formation of t-tubules started around day 9 (D9) as small membrane invaginations. Invaginations formed a loose network with predominating longitudinal elements around D14, and after D17 developed into a semi-regular tubular network. Cell size, area and membrane capacitance was increasing throughout the observed age interval and around D28 reached values typical for cells from adult rat hearts. During early development, calcium current density increased, saturating around D11. The rate of Ca-current decay increased with age, reaching values typical for adult myocytes after D10.These data suggest that functional local calcium signaling is present already at D11, when the t-tubules only start to form. This is supported especially by the dynamics of calcium current decay, which at D11 becomes as fast as in adult cardiac myocytes.Support: VEGA 2/0095/15 and VEGA 2/0147/14.