Role of dual pacemaker mechanisms in sinoatrial node discharge

Abstract

We investigated whether in the sinoatrial node (SAN) there are two different pacemaker mechanisms and whether either one can maintain spontaneous discharge. These questions were studied by means of an electrophysiological technique and of blockers of different diastolic currents in rabbit and guinea pig isolated SAN. In SAN subsidiary pacemakers of both species, Cs⁺ (5–10 mM) or high [K⁺]_o (10–12 mM) decreased the maximum diastolic potential, abolished diastolic depolarization (DD) at polarized levels (subsidiary DD), unmasked a U-shaped dominant DD at depolarized levels, but did not stop the SAN. In rabbit SAN, E4031 (1 µM) andd-sotalol (100 µM) did not stop discharge, but did so after block of subsidiary DD by high [K⁺]_o or Cs⁺. In guinea pig SAN, in Tyrode solution E4031,d-sotalol or indapamide (100 µM) did not stop SAN discharge. In the presence of Cs⁺ or high [K⁺]_o indapamide (but not E4031 ord-sotalol) stopped the SAN. Ba²⁺ (1–5 mM) led to stoppage of discharge both in Tyrode solution and in high [K⁺]_o or Cs⁺. Depolarization by blockers of DD unmasked sinusoidal fluctuations, which during recovery were responsible for resumption of discharge. We conclude that in rabbit and guinea pig SAN, two different pacemaker mechanisms (Cs⁺- and K⁺-sensitive subsidiary DD, and Cs⁺- and K⁺-insensitive dominant DD) can independently sustain discharge, but block of both mechanisms leads to quiescence. Abolition of dominant DD by blockers of I_K is consistent with a decay of I_K as the dominant pacemaking mechanism, I_Kr being more important in rabbit and I_Ks in guinea pig. Sinusoidal fluctuations appear to be an essential component of the pacemaking process.