Acetylcholine-dependent Prolongation Of Atrial Action Potentials By Acute Stretch

Abstract

Mechanical stretch of cardiomyocytes modulates the action potential (AP) via stretch-activated channels. The electrical activity is also modulated by the parasympathetic nervous system via the acetylcholine (ACh)-dependent potassium current. The ACh effect is however heterogeneous throughout the atria thus facilitating arrhythmic events. Simultaneous activation of both systems could occur and may facilitate atrial arrhythmias. Simulations of a canine atrial ionic model in an isolated cell and linear tissue strand were computed with varying stretch and ACh levels. Pacing at 1Hz, AP duration (APD) is increased (see APs in panel A) by ∼47 ms with 20% stretch compared to control (CTL). However, stretch did not increase APD in presence of 25 nmol/L of ACh (ACh vs. ACh+stretch in panel A). Restitution curves calculated with the S1-S2 protocol (S1=1 Hz) are plotted in panel B. Stretch (20%) results in an upshift of ∼47 ms of the restitution curve compared to CTL. ACh almost eliminate atrial restitution compared to CTL with no important changes with stretch (ACh vs. ACh+stretch curves). Preliminary results obtained in a cable with heterogeneous ACh distribution showed an increased interval for block of electrical propagation with tissue stretch.View Large Image | View Hi-Res Image | Download PowerPoint Slide