Sinoatrial Nodal (SAN) Cells from Center or Peripheral SAN Area are not Functionally Different

Abstract

SAN cells (SANC) determine the rate and rhythmicity of action potentials (AP) that emanate from the SAN to drive the heartbeat. Perspectives gleaned from SAN tissue have been interpreted to indicate that cells from the central SAN, i.e. smaller cells, control the SAN AP firing rate, while data from both SAN and isolated SANC argue that calcium cycling protein density is independent of SAN area and SANC size, and that spontaneous AP cycle length is independent of cell size. Since it is well documented that the gap junction protein, Connexin 43 (Cx43), is largely expressed in the peripheral vs. central SAN areas, we measured the properties of single SANC, employing Cx43 immunolabeling to distinguish cells isolated from the central (Cx43-negative) or peripheral (Cx43-positive) SAN areas.Freshly isolated adult rabbit SANC from the central area (Cx43-negative) are, on average, smaller (612.9±2.5μm2, n=340) than peripheral SANC (818.6±23.7μm2, n=188, p<0.001), but there is no difference in the spontaneous AP firing rate (3.07±0.13Hz, n=13, for Cx43-negative and 3.28±0.12Hz, n=23, for Cx43-positive). The AP amplitude and Maximum Diastolic Depolarization also did not differ, but compared to Cx43-positive SANC, the AP of Cx43-negative SANC has a slower AP upstroke (dV/dtmax (V/S): 8.12±1.31 vs. 13.4±0.62, p<0.001) and a longer repolarization time (APD75 (ms): 120.7±4.9 vs. 102.4±2.9, p<0.01). Linear regression analyses failed to detect any significant correlations between any AP parameter and the cell size for both. Preliminary data does not show significant differences between Cx43-positive or negative SANC in the AP triggered global Ca2+-transient or spontaneous diastolic Local Ca2+ Releases. Our results indicate that although different in size, single isolated central and peripheral SANC, in the basal state, are not functionally different from each other in respect to average spontaneous AP cycle length.