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Abstract

The endocardial endothelium is an important modulator of myocardial function. The present study demonstrates the existence of a stretch-activated Ca²⁺-permeable cation channel and of a Ca²⁺-activated K⁺ channel in the endocardial endothelium of the porcine right atrium. The stretch-activated channel is permeable for K⁺, Na⁺, Ca²⁺, and Ba²⁺, with mean conductances of approximately 32 pS for the monovalent cations and approximately 13 pS for divalent cations. The Ca²⁺-activated K⁺ channel has a mean conductance of 192 pS in symmetrical KCl. solution. Channel activity is strongly dependent on membrane potential and the cytosolic Ca²⁺ concentration. Half-maximal activation occurs at a cytosolic Ca²⁺ concentration of approximately 5 microM. The influx of Ca²⁺ through the stretch-activated channel is sufficient to activate the Ca²⁺-activated K⁺ channel in cell-attached patches. Upon activation of the stretch-activated channel, the cytosolic Ca²⁺ concentration increases, at least locally, to values of approximately 0.5 microM, as deduced from the open probability of the Ca²⁺-dependent K⁺ channel that was activated simultaneously. The stretch-activated channels are capable of inducing an intracellular Ca²⁺ signal and may have a role as mechanosensors in the atrial endothelium, possibly activated by atrial overload.