Key Points
- To characterize the fade in chronotropic slowing and investigate the kinetics of desensitization and recovery during exposure to acetylcholine in rabbit sino-atrial node tissue.
- Recorded spontaneous action potentials using glass microelectrodes in isolated rabbit sino-atrial node preparations mounted in a fast-flow bath to enable abrupt drug delivery.
- Assessed concentration-dependent fade across approximately 10⁻⁷ to 10⁻⁵ M acetylcholine using single exposures and conditioning-test dose protocols.
- Abrupt acetylcholine exposure initially increased cycle length, which then faded monophasically at low doses and biphasically at higher doses, exhibiting a fast half-time of 10 ± 2 s and a slow half-time of 240 ± 30 s (mean ± SEM; n = 5).
- Recovery from desensitization occurred with a half-time of 40 ± 8 s (mean ± SD; n = 8) after a 30 s conditioning dose and slowed to 250 ± 20 s (n = 6) after a 5 min exposure.
- Washout of acetylcholine caused an immediate post-exposure rebound where cycle length transiently shortened below baseline before recovering over several minutes.
Structured PICO
PPopulationSmall preparations of the sino-atrial node of the rabbit
IInterventionAcetylcholine (ACh) application (concentrations roughly 10^-7 to 10^-5 M)
OOutcomeFrequency of spontaneous action potentials (cycle length) and the fade of the chronotropic responsesurrogate
The chronotropic response to acetylcholine in the rabbit sino-atrial node exhibits a concentration-dependent fade that requires a fast flow bath to observe.