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Effects of dichlorobenzamil, a sodium-calcium exchange inhibitor, on the calcium paradox and the sodium withdrawal contractures of frog atrial muscle.

Abstract
1. The effects of dichlorobenzamil (DCB), an amiloride derivative and potent inhibitor of Na-Ca exchange in cardiac sarcolemmal vesicles and isolated cardiac myocytes, were investigated in two paradigms involving Na-Ca exchange, namely the Ca2+ paradox and the Na+-withdrawal contractures of frog atrial muscle strips. 2. Pretreatment with DCB (10-100 microM) inhibited in a dose-dependent manner the contractures elicited by reexposure of the atrial strips to the control Ringer solution after a 5-20 min equilibration with a Ca2+-free saline (Ca2+-readmission contractures; Ca2+ paradox). These contractures were not inhibited, however, when DCB was applied after the preparation had been exposed to the Ca2+-free saline, but before the reexposure to the control Ringer solution. 3. DCB (10-100 microM) did not inhibit the contractures elicited by Na+-deficient saline (Na+-withdrawal contractures) in atrial strips pretreated or not with acetylstrophantydin. This result suggests that, under our experimental conditions, DCB failed to substantially inhibit the Ca2+ influx mediated by Na-Ca exchange. 4. The duration of the plateau of the action potentials of atrial cells equilibrated with Ca2+-free saline was reduced from 1.42 +/- 0.27 s to 0.61 +/- 0.13 s by 50 microM DCB (P less than 0.001). This was attributed to blockade of Na+ currents through modified L-type Ca2+ channels. 5. It is proposed that the shortening of the Na+-dependent action potentials can account for the inhibition of the Ca2+-readmission contractures, because these contractures have a steep dependence on the Na+ influx and intracellular Na+ accumulation that occurs during the Ca2+-free period. 6. The results of this study support the conclusion that DCB has multiple effects on heart muscle, including a potent blockade of Ca2+ channels, and its use as a selective inhibitor of Na-Ca exchange in cellular systems is unwarranted.
AuthorsG Suarez-Kurtz, T Sollero, J H Leal-Cardoso, G Kaczorowski
JournalBrazilian journal of medical and biological research = Revista brasileira de pesquisas médicas e biológicas / Sociedade Brasileira de Biofísica ... [et al.] (Braz J Med Biol Res) Vol. 21 Issue 6 Pg. 1197-211 ( 1988) ISSN: 0100-879X [Print] BRAZIL
PMID3074842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Calcium Channel Blockers
  • Amiloride
  • Sodium
  • Calcium
Topics
  • Amiloride (analogs & derivatives)
  • Animals
  • Anura
  • Binding, Competitive
  • Calcium (metabolism, pharmacology)
  • Calcium Channel Blockers (pharmacology)
  • Electric Stimulation
  • Electrophysiology
  • Heart Atria (drug effects)
  • Ion Exchange
  • Myocardial Contraction (drug effects)
  • Sodium (metabolism, pharmacology)

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