Steady-state and dynamic properties of cardiac sodium-calcium exchange: Ion and voltage dependencies of the transport cycle

Satoshi Matsuoka, Donald W. Hilgemann

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Abstract

Ion and voltage dependencies of sodium-calcium exchange current were studied in giant membrane patches from guinea pig ventricular cells after deregulation of the exchanger with chymotrypsin. (a) Under zero-trans conditions, the half-maximum concentration (Kh) of cytoplasmic calcium (Cai) for activation of the isolated inward exchange current decreased as the extracellular sodium (Nao) concentration was decreased. The Kh of cytoplasmic sodium (Nai) for activation of the isolated outward exchange current decreased as the extracellular calcium (Cao) concentration was decreased, (b) The current-voltage (I-V) relation of the outward exchange current with saturating concentrations of Nai and Cao had a shallow slope (twofold change in ∼ 100 mV) and a slight saturation tendency at very positive potentials. The outward current gained in steepness as the Nai concentration was decreased, such that the Kh for Nai decreased with depolarization. The decrease of Kh for Nai with depolarization was well described by a Boltzmann equation (eα·Em/26.6) with a slope (α) of -0.06. (c) Voltage dependence of the outward current was lost as the Cao concentration was decreased, and the Kh for Cao increased upon depolarization with a Boltzmann slope of 0.26. (d) The I-V relation of the inward exchange current, under zero-trans conditions, was also almost linear (twofold change in ∼ 100 mV) and showed some saturation tendency with hyperpolarization as the Cai concentration was decreased. The Kh for Cai decreased with depolarization (Boltzmann slope, -0.10). Voltage dependence of the inward current was decreased in the presence of a high (300 mM) Nao concentration, (e) In the presence of both Na and Ca on both membrane sides, the I-V relations with saturating Nai show sigmoidal shape and clear saturation at positive potentials. Measured reversal potentials were close to the equilibrium potential expected for a 3 Na to 1 Ca exchange. (f) Nai and Cai interacted competitively with respect to the outward current, but in a mixed competitive-noncompetitive fashion with respect to the inward current, (g) Cai inhibited the outward exchange current in a voltage-dependent manner. The half-effective concentration for inhibition (Ki) by Cai increased upon depolarization with a Boltzmann slope of 0.32 in 25 mM Nai and Similar to the effects of cytoplasmic calcium, MgATP slows the entrance into I1 inactivation and accelerates the recovery from inactivation. MgATP additionally slows the decay of outward exchange current upon removal of cytoplasmic calcium by 2-10-fold, indicative of an effect on I2 inactivation. Finally, the effects of cytoplasmic calcium on sodium-calcium exchange current are reconstructed in simulations of the I1 and I2 modulation processes as independent reactions.

Original languageEnglish (US)
Pages (from-to)963-1001
Number of pages39
JournalJournal of General Physiology
Volume100
Issue number6
StatePublished - Dec 1992

ASJC Scopus subject areas

  • Physiology

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