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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/C1374    most recent 00492.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Beaugé, L. Articles by DiPolo, R. Search for Related Content PubMed PubMed Citation Articles by Beaugé, L. Articles by DiPolo, R.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

SEA-0400, a potent inhibitor of the Na⁺/Ca²⁺ exchanger, as a tool to study exchanger ionic and metabolic regulation

¹Laboratorio de Biofísica, Instituto de Investigaciones Médicas Mercedes y Martin Ferreira, Córdoba, Argentina; and ²Laboratorio de Permeabilidad Ionica, Instituto Venezolano de Investigaciones Científicas, Centro de Biofísica y Bioquímica, Caracas, Venezuela, and Marine Biological Laboratory, Woods Hole, Massachusetts

Submitted 12 October 2004 ; accepted in final form 13 January 2005

The effects of a new, potent, and selective inhibitor of the Na⁺/Ca²⁺ exchange, SEA-0400 (SEA), on steady-state outward (forward exchange), inward (reverse exchange), and Ca²⁺/Ca²⁺ transport exchange modes were studied in internally dialyzed squid giant axons from both the extra- and intracellular sides. Inhibition by SEA takes place preferentially from the intracellular side of the membrane. Its inhibition has the following characteristics: it increases synergic intracellular Na⁺ (Na_i⁺) + intracellular H⁺ (H_i⁺) inactivation, is antagonized by ATP and intracellular alkalinization, and is enhanced by intracellular acidification even in the absence of Na⁺. Inhibition by SEA is still present even after 1 h of its removal from the experimental solutions, whereas removal of the cointeracting agents of inhibition, Na_i⁺ and H_i⁺, even in the continuous presence of SEA, releases inhibition, indicating that SEA facilitates the reversible attachment of the natural H_i⁺ and Na_i⁺ synergic inhibitors. On the basis of a recent model of squid Na⁺/Ca²⁺ exchange regulation (DiPolo R and Beaugé L. J Physiol 539: 791–803, 2002), we suggest that SEA acts on the H_i⁺ + Na_i⁺ inactivation process and can interact with the Na⁺-free and Na⁺-bound protonized carrier. Protection by ATP concurs with the antagonism of the nucleotide by H_i⁺ + Na_i⁺ synergic inhibition.

ionic-metabolic interactions

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