Changes in the fluctuation of interbeat intervals in spontaneously beating cultured cardiac myocytes: experimental and modeling studies

 Isolated and cultured neonatal cardiac myocytes contract spontaneously and cyclically, and have the properties of a non-linear oscillator. In this study, we have analyzed the relationship between the fluctuation of contraction rhythm of spontaneously beating cultured cardiac myocytes, and the coupling strength among them. The coefficient of variation of contraction intervals increased transiently in the early stages of incubation, and then decreased almost monotonically with time. The contraction rhythm of the myocytes became synchronized in the late stage of the culture. The day on which synchronization occurred almost coincided with the day when the coefficient of variation reached its lowest value. In addition, we have performed a mathematical analysis using interacting Bonhoeffer–van der Pol oscillators to clarify the mechanisms underlying the changes in the fluctuation of contraction rhythm with time. As the coupling strength among oscillators increased, the coefficient of variation of oscillation periods increased temporarily, but then decreased rapidly when the oscillators showed synchronization. These results suggest that the changes in the fluctuation of beating rhythm result from the increase in strength of electrical coupling among spontaneously beating cardiac myocytes. Received: 10 August 2000 / Accepted in revised form: 19 August 2001