Electrophysiological heterogeneity of pacemaker cells in the rabbit intercaval region, including the SA node: insights from recording multiple ion currents in each cell.

Cardiac pacemaker cells, including cells of the sinoatrial node, are heterogeneous in size, morphology, and electrophysiological characteristics. The exact extent to which these cells differ electrophysiologically is unclear yet is critical to understanding their functioning. We examined major ionic currents in individual intercaval pacemaker cells (IPCs) sampled from the paracristal, intercaval region (including the sinoatrial node) that were spontaneously beating after enzymatic isolation from rabbit hearts. The beating rate was measured at baseline and after inhibition of the Ca pump with cyclopiazonic acid. Thereafter, in each cell, we consecutively measured the density of funny current ( I), delayed rectifier K current ( I) (a surrogate of repolarization capacity), and L-type Ca current ( I) using whole cell patch clamp The ionic current densities varied to a greater extent than previously appreciated, with some IPCs demonstrating very small or zero I . The density of none of the currents was correlated with cell size, while I and I densities were related to baseline beating rates. I density was correlated with I density but not with that of I. Inhibition of Ca cycling had a greater beating rate slowing effect in IPCs with lower I densities. Our numerical model simulation indicated that 1) IPCs with small (or zero) I or small I can operate via a major contribution of Ca clock, 2) I-Ca-clock interplay could be important for robust pacemaking function, and 3) coupled I- I function could regulate maximum diastolic potential. Thus, we have demonstrated marked electrophysiological heterogeneity of IPCs. This heterogeneity is manifested in basal beating rate and response to interference of Ca cycling, which is linked to I. NEW & NOTEWORTHY In the present study, a hitherto unrecognized range of heterogeneity of ion currents in pacemaker cells from the intercaval region is demonstrated. Relationships between basal beating rate and L-type Ca current and funny current ( I) density are uncovered, along with a positive relationship between I and delayed rectifier K current. Links are shown between the response to Ca cycling blockade and I density.