Abstract Stretch of the cardiac muscle activates several physiological processes leading to changes in the function of the muscle. These changes include increase of the contraction force accompanied by changes in the intracellular calcium concentration. This phenomenon is known as Frank-Starling relation of the heart. In addition to this, stretch also influences the membrane voltage of individual myocytes predisposing the cardiac muscle to arrhythmias. In atrial muscle stretch augments the secretion of the atrial natriuretic peptide (ANP). Although several cellular components are known to be sensitive to mechanical stimulus the precise mechanisms participating to these stretch-induced changes are not known in detail. Further it is not known if these changes are causally related or if they share a common causal factor. This research was aimed to study the stretch-induced changes in the rat atrium. The possible interactive mechanisms were studied by recording intracellular action potentials, changes in the intracellular calcium concentration, contraction force and ANP secretion during stretch. The plausible mechanosensitive cellular components were incorporated into a mathematical model that was used to further study the mechanisms. The role of intracellular acidosis as a possible modulator of the mechanotransduction was of special interest. In isolated rat left atrium moderate stretch produced by increasing the intra-atrial pressure increased the contraction force in a biphasic manner. The immediate increase of the force was caused by altered properties of the contractile element, but the following slow increase was accompanied by an increase of the Ca2+ transient. These changes were followed by lengthening of the late phase of action potentials and augmented secretion of the ANP. Intensive sustained stretch was also found to induce delayed afterdepolarizations (DADs). Gadolinium (Gd3+), blocker of stretch-activated ion channels reduced the stretch-dependent activation of the contraction and inhibited the stretch-induced DADs. The mathematical model simulated the experimental findings at best when stretch-activated channel (SA-channel) activation and increased troponin-C affinity were used to mimic the stretch. The modelling data suggested that the SA-channel current increases the sarcoplasmic reticulum calcium content in a time dependent manner leading to Ca2+ transient augmentation during systole. Bigger Ca2+ transients induce a depolarizing current during the late phase of the action potential (AP) repolarization via the Na+/Ca2+ exchanger causing the lengthening of the action potentials. A small reduction of the intracellular pH (0.18 units) with 20 mM propionate was found to modulate the stretch-induced changes in the rat atrium. Acidosis leads to an increase in the diastolic [Ca2+]i during stretch, inhibits the stretch-induced changes in action potentials and slows down the contraction development during stretch by inhibiting the fast component of the force increase. These changes in E-C-coupling (excitation-contraction-coupling) were accompanied by a simultaneous augmentation of the ANP secretion. Furthermore, it was shown that contraction force and diastolic [Ca2+]i of the stretched tissue are more sensitive to acidosis than in non-stretched tissue. In conclusion, the stretch-induced changes in rat atrial myocytes are mediated by at least two mechanisms; stretch-activated Ca2+ influx and change in the properties of the contractile element. The action potential changes can be largely explained by modulation of the membrane voltage by intracellular calcium via Na+/Ca2+-exchanger. The co-occurrence of the changes in the [Ca2+]i and ANP secretion suggests that the stretch-induced ANP secretion can be mediated by [Ca2+]i.