title: Regulation kinetics of Na+-Ca2+ exchange current in guinea-pig ventricular myocytes.
abstract: To investigate the regulation of native cardiac Na+-Ca2+ exchange by cytoplasmic Na+ (Na+i) and Ca2+ (Ca2+i), we recorded the Na+-Ca2+ exchange current (INa-Ca) from inside-out 'macro patches' excised from intact guinea-pig ventricular cells. The half-maximal concentration (Kh) of Ca2+i required to induce an inward INa-Ca was 7 microM. The Kh of Na+i required to induce an outward INa-Ca was 21 mM, and tended to decrease at the steady state of Na+-dependent inactivation. The time constant (tau) of Na+-dependent inactivation was approximately 1.5 s at 100 mM Na+i and 1 microM Ca2+i. The Kh for Na+i was 14 mM. Ca2+i augmented the peak outward INa-Ca (Kh = 0. 2 microM) and attenuated Na+-dependent inactivation (Kh = 2.2 microM). The outward INa-Ca was activated by 5 microM Ca2+i with a half-time to reach steady state (t1/2) of approximately 0.4 s. This activation was composed of two exponential processes. Deactivation of the current upon Ca2+i removal also consisted of two exponential processes and had a t1/2 of approximately 0.5 s. A Na+-Ca2+ exchange model, consisting of one consecutive 4Na+:1Ca2+ exchange cycle and two inactive states, well mimicked the experimental data with regard to ion dependencies and regulation kinetics. These data provide detailed information on the kinetics of the Na+i- and Ca2+i-dependent regulation of native Na+-Ca2+ exchange. They also indicate that the regulation kinetics operate faster in macro patches than in the giant membrane patch from cardiac 'blebs', or in Xenopus oocytes expressing a cloned exchanger (NCX1.1).
authors.affiliation: Department of Physiology and Biophysics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujioka
authors.forename: K
authors.initials: K
authors.lastname: Hiroe
authors.forename: S
authors.initials: S
authors.lastname: Matsuoka
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D004553:Electric Conductivity; D006168:Guinea Pigs; D007477:Ions; D007700:Kinetics; D009206:Myocardium / Q000166:cytology; D012964:Sodium / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D016276:Ventricular Function / Q000502:physiology*
chemical_list: D007477:Ions; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium