Role of the input/output relation of sinoatrial myocytes in cholinergic modulation of heart rate variability

Input/Output Relation of the Sinoatrial Node, Introduction: Modulation of s inus rate may be viewed as the transduction of an input signal (receptor st imulation) into an output signal (cycle length [CLI) by the sinus node. Thi s study analyzes the input/output (I/O) relation of sinoatrial pacemaking e lements and tests its impact on cholinergic modulation of heart rate variab ility. Methods and Results: Spontaneous activity of isolated rabbit sinoatrial myo cytes was recorded by patch clamp techniques. CL and all the action potenti al parameters determining CL were automatically measured from >100 consecut ive cycles, Acetylcholine (ACh, 5 to 50 nM) increased CL by decreasing dias tolic depolarization rate (DDR) only. This was associated with a substantia l increase in the coefficient of variation of CL and minor changes in the c oefficient of variation of other parameters. A simple function relating CL to action potential parameters accurately described CL response to ACI (I/O relation). Numerical simulations based on this I/O relation showed that AC h-induced depression of DDR might, by its own, increase CL variability. Conclusion: Time-domain measurements of CL variability may not necessarily reflect variability of the neural input to the sinoatrial node, but also ma y be affected by its tonic level. Properties of the I/O relation of sinoatr ial myocytes may fully account for the dependency of CL variability on mean heart rate, previously described in humans. Any condition depressing DDR m ay enhance CL variability, independent of changes in the pattern of neural activity.