Role of the Input/Output Relation of Sinoatrial Myocytes in Cholinergic Modulation of Heart Rate Variability

hv viewed as the transduction of an input signal (receptor stimulation ) into an output .signal (cyclelength ICLi) by the sinus node. This study analyzes the input/output (I/O) rt-lation of .sinoatrialpacemaking elements and tests Its impact on choiinergic modulation of rate variahility.Methods and Results: Spontaneous activity of isolated rabbit sinoatrial myocytes was recorded bypatch clamp techniques. CL mid all tbe action potential parameters determining CL were autonuit-icaUy measured from >l«0 consecutive cycles. Acetylcboline (Atb. 5 to 50 nM) increased CL bydecreasing diastolic depolarization rate (I)I)R) only. This was associated with a substantial increasein tbe coefTieient of variation of CL and minor cbanges in tbe eoeflicient of variation of otherparameters. A simple function relating CL to action potential parameters accurately described CLresptmse to ACh (I/O relation). Numerical simulations based on this I/O relation showed thatACh-indui-ed depre.s.sion of DDR might, by its own, increase CL variability.Conclttsion: I ime-domain measurements of CL variability may not necessarily reflect variabilityof tbe neural input to tbe sinoatrial node, but also may be affected by its tonic level. Properties ofthe I/O relation of sinoatrial myocytes may fully account for the dependency of CL variability onmean beart rate, previously described in bumans. Any condition depressing DDR may enhance CLvariability, independent of changes in tbe pattern of neural activity. (J Curdiovasc Electrophysiol, Vol.II, pp. 522-530. May 2(HX))sinu.s node, rate variahilitY, acetxicholine. autonomic nervous svstemIntroductionThe pacemaker activity of the sinoatrial node is sub-ject to infiuence of neural, endocrine, and mechanicalfactors. Such input signals are transduced by the sinusnode to set the cycle length (CL) of pacemaker dis-charge. The temporal variability of sinoatrial CL. oftenloosely referred to as heart rate variability. is widelyexploited as an indirect measure of such inputs, particu-larly of sympathetic and vagal outflows.' However, therelation between sinus node input (e.g.. neural discharge)and output (CL) signals has never been characterized.