Species- and preparation-dependence of stretch effects on sino-atrial node pacemaking

Acute dilation of the right atrium (e.g., via increased venous return) raises spontaneous beating rate (BR) of the heart in many species. Neural mechanisms contribute to this behavior in vivo, but a positive chronotropic response to stretch can also be observed in isolated right atrial tissue preparations and even at the level of single sino-atrial node (SAN) cells. The underlying mechanism has previously been reported to be compatible with stretch-activation of cation nonselective ion channels (SAC). This review reports species peculiarities in the chronotropic response of isolated SAN tissue strips to stretch: in contrast to guinea pig, murine SAN preparations respond to distension with a reduction in spontaneous BR. This differential response need not necessarily involve disparate (sub-)cellular mechanisms, as SAC activation would occur against the background of very different SAN electrophysiology in the two species. On the basis of single SAN cell action potential recordings, this review illustrates how this may give rise to potentially opposing effects on spontaneous BR. Interestingly, streptomycin (a useful SAC blocker in isolated cells) has no effect on stretch-induced chronotropy in situ, and this is interpreted as an indication of protection of SAC, in native tissue, from interaction with the drug.