The effect of block of the L-type Ca2+ current by 2 microM nifedipine and of the Na+ current by 20 microM tetrodotoxin on the center (normally the leading pacemaker site) and periphery (latent pacemaker tissue) of the rabbit sinoatrial node was investigated. Spontaneous action potentials were recorded with microelectrodes from either an isolated right atrium containing the whole node or small balls of tissue (approximately 0.3-0.4 mm in diameter) from different regions of the node. Nifedipine abolished the action potential in the center, but not usually in the periphery, in both the intact sinoatrial node and the small balls. Tetrodotoxin had no effect, on electrical activity in small balls from the center, but it decreased the takeoff potential and upstroke velocity and slowed the spontaneous activity (by 49 +/- 10%; n = 11) in small balls from the periphery. It is concluded that whereas the L-type Ca2- current plays an obligatory role in pacemaking in the center, the Na+ current plays a major role in pacemaking in the periphery.
Ranolazine inhibits shear sensitivity of endogenous Na+current and spontaneous action potentials in HL-1 cells