CA2+ INFLUX THROUGH STRETCH-ACTIVATED CATION CHANNELS ACTIVATES MAXI K+ CHANNELS IN PORCINE ENDOCARDIAL ENDOTHELIUM

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 approximate to 32 pS for the monovalent cations and approximate to 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 approximate to 5 mu M. 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 approximate to 0.5 mu M, 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.