Although KATPchannels have been proposed as playing a role in most types of myocardial damage associated with ischemia/reperfusion, the potential benefits of KATPchannel modulators against the biochemical and electrical disturbances observed during ischem

The present study demonstrates that background or B-type calcium channel activity can be recorded in excised inside-out and cell-attached membrane patches from human atrial myocytes. In control conditions, with Ba2+or Ca2+as charge carrier, single-channel activity spontaneously appeared in irregular bursts separated by quiescent periods of 2–17 min, in nearly 25% of tested patches. Channel activity was recorded at steady-state applied membrane potentials including the entire range of physiological values, and displayed no “rundown” in excised patches. During activity, a variety of kinetic behaviors could be observed with more or less complex gating patterns. This type of channel activity was triggered or markedly increased when chlorpromazine (CPZ 20 or 50μ ) was applied to internal face of inside-out patches, with a proportion of active patches of ≈25%. CPZ-activated channels were potential-independent in the physiological range of membrane potential. In 96 m Ba2+solution, three conductance levels: 23, 42 and 85 pS were routinely observed in the same excised membrane patch, sometimes combining to give a larger level. As previously observed by Wanget al. (1995) in membrane of rat ventricular myocytes, increasing free-radicals level and metabolic poisoning readily enhanced B-type channel activity in human atrial myocytes. Application of H2O2(from 0.1–10 m ) in cell-attached mode induced an activation of Ba2+permeable channel activity in a dose-dependent manner, with an estimated EC50of 9.7 m . In the same type of experiments, 10 m deoxyglucose also induced similar Ba2+permeable channel activity. When 500μ CPZ were applied to myocytes studied in the whole-cell configuration and maintained at a holding potential of −80 mV in the presence of 5 m external Ca2+, a noticeable inward current could be observed. The mean CPZ-activated current density, determined from seven myocytes was 0.63 pA/pF.