Study on ion transport of cardiac Na^+-K^+ pump and Na^+-Ca^<2+> exchnage

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1. We successfully developed a method to excise macro-patch from intact cardiac ventricular cells and recorded Na^+-Ca^<2+> exchange (I_<Na/Ca>) and Na^+-K^+ pump currents (cardiac cell macro-patch method).2. We studied stoichiometry of Na^+-Ca^<2+> exchange using the cardiac cell macro-patch method by determining reversal potentials of I_<Na/Ca>. The stoichiometry was approximately 4Na^+ : 1Ca^<2+>, which was different from currently-accepted 3Na^+ : 1Ca^<2+>. It was suggested that the stoichiometry gets close to 3Na^+ : 1Ca^<2+> as cytoplasmic Na^+ decreases to less than 5 mM.3. We studied regulation by cytoplasmic Na^+ and Ca^<2+> of I_<Na/Ca> in the macro-patch. Kinetics of Na^+ dependent inactivation was about two-fold faster than the exchanger in blebs and the one expressed in oocytes. Ca^<2+> activation was about ten times faster. We proposed that the Ca^<2+> regulation functions in a beat-to-beat manner in beating cells.4. We developed a mathematical Na^+-Ca^<2+> exchange model … More , based on the macro-patch data. The model can well simulate Na^+ and Ca^<2+> dependences, the Na^+ dependent inactivation and the activation by Ca^<2+>.5. We studied contribution of Na^+-Ca^<2+> exchange in a beating heart cell by computer simulation. At resting membrane potential, the majority of Na^+-Ca^<2+> exchange was in inactive states and does not function. The exchanger returns to the active state as intracellular Ca^<2+> transient occurs and functions in a forward mode. The exchanger enters the inactive states as intracellular Ca^<2+> concentration declines.6. In voltage-clamped ventricular cells, we successfully recorded charge movement associated with the Na^+ translocation of Na^+-K^+ pump by a rapid extracellular Na^+ concentration jump. Charge movement associated with the Ca^<2+> translocation could also be recorded by an extracellular K^+ jump. The total charge of K^+ translocation was about 1/4 of the one of Na^+ translocation. It was indicated that the K^+ translocation step is voltage sensitive as well as Na^+ translocation step. Less