Abstract
We investigated how Ca2+-sensitive transient outward current, I to(Ca), is activated in rabbit ventricular myocytes in the presence of intracellular Na+ (Na+ i) using the whole-cell patch-clamp technique at 36°C. In cells dialysed with Na+-free solutions,the application of nicardipine (5 µM) to block L-type Ca2+ current (I Ca) completely inhibited I to(Ca). In cells dialysed with a [Na+]i≥5 mM, however, I to(Ca) could be observed after blockade of I Ca, indicating the activity of an I Ca-independent component. The amplitude of I Ca-independent I to(Ca) increased with voltage in a [Na+]i-dependent manner. The block of Ca2+ release from the sarcoplasmic reticulum by caffeine, ryanodine or thapsigargin blocked I Ca-independent I to(Ca). In Ca2+-free bath solution I to(Ca) was completely abolished. The application of 2 mM Ni2+ or the newly synthesized compound KBR7943, a selective blocker of the reverse mode of Na+/Ca2+ exchange, or perfusion with pipette solution containing XIP (10 µM), a selective blocker of the exchanger, blocked I Ca-independent I to(Ca). From these results we conclude that, in the presence of Na+ i, I to(Ca) can be activated via Ca2+-induced Ca2+ release triggered by Na+/Ca2+ exchange operating in the reverse mode after blockade of I Ca.
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Received: 20 January 1998 / Received after revision: 6 July 1998 / Accepted: 25 July 1998
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Kuruma, A., Hiraoka, M. & Kawano, S. Activation of Ca2+-sensitive Cl– current by reverse mode Na+/Ca2+ exchange in rabbit ventricular myocytes. Pflügers Arch 436, 976–983 (1998). https://doi.org/10.1007/s004240050732
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DOI: https://doi.org/10.1007/s004240050732