Role of the input/output relation of sinoatrial myocytes in cholinergic modulation of heart rate variability.
BACKGROUND
Modulation of sinus rate may be viewed as the transduction of an input signal (receptor stimulation) into an output signal (cycle length [CL]) by the sinus node. This study analyzes the input/output (I/O) relation of sinoatrial pacemaking elements and tests its impact on cholinergic modulation of heart rate variability.


RESULTS
Spontaneous activity of isolated rabbit sinoatrial myocytes was recorded by patch clamp techniques. CL and all the action potential parameters determining CL were automatically measured from >100 consecutive cycles. Acetylcholine (ACh, 5 to 50 nM) increased CL by decreasing diastolic depolarization rate (DDR) only. This was associated with a substantial increase in the coefficient of variation of CL and minor changes in the coefficient of variation of other parameters. A simple function relating CL to action potential parameters accurately described CL response to ACh (I/O relation). Numerical simulations based on this I/O relation showed that ACh-induced depression of DDR might, by its own, increase CL variability.


CONCLUSIONS
Time-domain measurements of CL variability may not necessarily reflect variability of the neural input to the sinoatrial node, but also may be affected by its tonic level. Properties of the I/O relation of sinoatrial myocytes may fully account for the dependency of CL variability on mean heart rate, previously described in humans. Any condition depressing DDR may enhance CL variability, independent of changes in the pattern of neural activity.
Rocchetti
M
M
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Milan, Italy.
Malfatto
G
G
Lombardi
F
F
Zaza
A
A
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018678:Cholinergic Agents / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014741:Video Recording
D018678:Cholinergic Agents; D014665:Vasodilator Agents; D000109:Acetylcholine