The incidence of
atrial fibrillation correlates with increasing atrial size. The electrical consequences of atrial stretch contribute to both the initiation and maintenance of
atrial fibrillation. It is suggested that altered
calcium handling and stretch-activated channel activity could explain the experimental findings of stretch-induced depolarisation, shortened refractoriness, slowed conduction and increased heterogeneity of refractoriness and conduction. Stretch-activated channel blocking agents protect against these pro-arrhythmic effects.
Gadolinium,
GsMTx-4 toxin and
streptomycin prevent the stretch-related vulnerability to
atrial fibrillation without altering the drop in refractory period associated with stretch. Changes the activity of two-pore K+ channels, which are sensitive to stretch and pH but not
gadolinium, could underlie the drop in refractoriness. Intracellular
acidosis induced with
propionate amplified the change in refractoriness with stretch in the isolated rabbit heart model in keeping with the clinical observation of increased propensity to
atrial fibrillation with
acidosis. We propose that activation of non-specific
cation stretch-activated channels provides the triggers for acute
atrial fibrillation with high atrial pressure while activation of atrial two-pore K+ channels shortens atrial refractory period and increases heterogeneity of refractoriness, providing the substrate for
atrial fibrillation to be sustained. Stretch-activated channel blockade represents an exciting target for future
antiarrhythmic drugs.