Mutual entrainment and electrical coupling as mechanisms for synchronous firing of rabbit sino-atrial pace-maker cells.

The mechanisms of synchronous firing of cardiac pace-makers were studied using thin (0.3-0.5 mm) rabbit sino-atrial (s.a.) node strips placed in a three-compartment tissue bath. Superfusion of the central segment (1 mm in length) with ion-free sucrose solution permitted the electrical insulation of the external segments and the development of two independent pace-maker 'centres': one fast (F); one slow (S). An external shunt pathway was used to modulate the degree of coupling between F and S. Superfusion of the central segment with Tyrode solution containing heptanol (3.5 mM) instead of sucrose induced progressive decrease in the amplitude of responses in this segment and led to progressive loss of F:S synchronization. Eventually the two pace-makers became totally independent from each other. These changes were reversible upon wash-out of heptanol. When a pace-maker centre was within the range of influence of local circuit (i.e. electronic) currents from the pace-maker in the opposite side of the sucrose (or heptanol) compartment, its period was prolonged or abbreviated, depending on phase and frequency relations. Dynamic F:S interactions at various degrees of electrical coupling resulted in mutual entrainment with both pace-makers beating at simple harmonic (i.e. 1:1, 2:1, 1:2, etc.) or more complex (3:2, 5:4, etc.) ratios that depended on the degree of coupling and the intrinsic periods of the individual pace-maker centres. The patterns of synchronization could be predicted by the phasic sensitivity of each pace-maker to brief electrotonic inputs. The results suggest that when two individual pace-maker cells are connected through low resistance junctions, the period resulting from their mutual entrainment should be a function of their respective intrinsic frequencies, their phase relations and the degree of electrical coupling. The data further suggest that the heart beat is initiated by a 'democratic' type of synchronous firing of cells in the s.a. node, with each pace-maker cell contributing to an aggregate signal and involving mutual entrainment between cells.