In the squid axon Na/Ca exchanger the state of the Ca(i)-regulatory site influences the affinities of the intra- and extracellular transport sites for Na and Ca.

DIPOLO R. AND BEAUGÉ, L.

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY

Año: 2008 vol. 456 p. 623 - 633

0031-6768

In squid axons, intracellular Mg2+ reduces the activity of the Na+/Ca2+ exchanger by competing with Ca2+i for its regulatory site. The state of the Cai-regulatory site (active-inactive) also alters the apparent affinity of intra- and extracellular transport sites. Conditions that hinder the binding of Ca2+i (low pHi, low [Ca2+]i, high [Mg2+]i) diminish the apparent affinity of intracellular transport sites, in particular for Nai due to its synergism with H+ inhibition, but less noticeably for Ca2+i because of its antagonism towards (H+i+Na+i) and Mg2+i inhibitions. These are kinetic effects unrelated to the true affinity of the sites. With the Cai-regulatory site saturated, the intracellular transporting sites are insensitive to [H+]i and to ATP. Likewise, the state of the Cai-regulatory site (activated or inactivated) influences the affinity of the extracellular Cao and Nao-transport sites (trans effects). In this case, the effects are opposite to those predicted by any of the transport schemes proposed for the Na+/Ca2+ exchanger; i.e. its mechanism remains unexplained. In addition to their intrinsic importance for a full understanding of the properties of the Na+/Ca2+ exchanger, these findings show a new way by which the state of the Cai-regulatory site may determine net movements of Ca2+ through this system.