The mechanical response of the heart to myocardial stretch has been understood since the work of muscle physiologists more than 100 years ago, whereby an increase in ventricular chamber filling during diastole increases the subsequent force of contraction. The stretch-induced increase in contraction is biphasic. There is an abrupt increase in the force that coincides with the stretch (the rapid response), which is then followed by a slower response that develops over several minutes (the slow force response, or SFR). The SFR is associated with a progressive increase in the magnitude of the Ca2+ transient, the event that initiates myocyte cross-bridge cycling and force development. However, the mechanisms underlying the stretch-dependent increase in the Ca2+ transient are still debated. This review outlines recent literature on the SFR and summarizes the different stretch-activated Ca2+ entry pathways. The SFR might result from a combination of several different cellular mechanisms initiated in response to activation of different cellular stretch sensors.
Keywords: Autocrine/paracrine response; Calcium influx; Cardiac stretch; G-coupled protein receptors; Slow force response; Stretch-activated channels.