Heterogeneity in Beating and Response to Beta Adrenergic Receptor Stimulation in Isolated Single Sinoatrial Nodal Cells (SANC)

Abstract

Studies of enzymatically isolated single SANC have greatly expanded our knowledge of pacemaker mechanisms. Beating rate and rhythms of isolated SANC vary, but only those SANC with the presence of rhythmic beating are routinely chosen for study. Here we examined responses of varieties of healthy appearing rabbit SANC to beta-adrenergic receptor stimulation(BARs). Videos of SANC were recorded to monitor spontaneous beating before and during BARs (isoproterenol, 1-1000nM). Sixty percent of 58 apparently healthy SANC did not exhibit any beating over 30 minutes of observation (time-control). BARs converted 32% of 71 non-beating SANC to beating, suggesting that a subpopulation of dormant cells was dormant not due to “stunning” by isolation, but that it represents dormant cells capable of generating rhythmic beating in response to BARs. In fact, some dormant SANC after BARs beat at a rate as fast as, or even faster than those SANC beating prior to BARs. Moreover, SANC with rhythmic beating following isolation responded differently to BARs, including large, moderate, small and even no responses in beating rate at all. Thus, we discovered that single, isolated SANC substantially differ from each other, not only by their shape and ion channel expression (also see poster Monfredi et al.), but also by their beating and scale of response to BARs. Were this variable behavior of isolated SANC to be indeed present in the SA node in vivo, it would indicate that cells differ in their contribution to the SA node generating basal AP firing rate and the response to BARs, and thus, this cell heterogeneity may be implicated in shifts in primary SA node pacemaker site in response to autonomic receptor stimulation.