Acute effects of sodium selenite on the isolated mouse diaphragm and in the anesthetized rat

Yadhu N. Singh, Terrance J. Adam, Lori A. Lulf, Jess J. Hanson

Research output: Contribution to journalArticle

Abstract

The effects of sodium selenite on neuromuscular transmission, muscle contractility and cardiovascular functions were studied in the isolated mouse phrenic nerve-hemidiaphragm preparation and the anesthetized rat. Sodium selenite (3x10-5 -10-4 M) augmented, then blocked, contractions of the diaphragm induced directly or indirectly by trains of 75 Hz of 0.1 see duration and supramaximal voltage, given every 20 sec. In higher concentrations (3x10-4 -10-3 M), only blockade of contraction was obtained. The later stages of onset of muscle paralysis were accompanied by the development of a contracture whose amplitude was dose-dependent. Pretreatment with elevated Ca2+ (8-12 mM) significantly decreased the degree of neuromuscular block, while low Ca2+ (0.5 mM) had little effect. Glutathione (2-4 mM) also protected against selenite-induced depression of contraction. Elevated Ca2+ or glutathione were less or not effective when they were added after onset of selenite activity. The amplitude of selenite- induced contractures was not affected by reduction of extracellular Ca2+ to 10-6 M, but if ethyleneglycol-bis-(β-amino-ethyl ether)-N,N'-tetraacetic acid (EGTA, 5-15 mM) was also present, peak tension was significantly reduced. In the anesthetized rat, infusion of the sodium selenite had a deleterious effect on blood pressure, heart rate and EKG without significantly affecting neuromuscular transmission in the tibialis anterior muscle. The findings suggest that selenite ions augment muscle contraction by increasing transmitter release and a direct myogenic action, followed by a block induced by selenite binding to membrane sulthydryl groups. A subsequent muscle contracture is probably caused by Ca2+ released from the sarcoplasmic reticulum. In the rat, effects on cardiovascular parameters were more dramatic than on skeletal muscle, suggesting that effects on the cardiovascular system play an important role in selenite induced respiratory failure in vivo.

Original languageEnglish (US)
Pages (from-to)351-360
Number of pages10
JournalJournal of Natural Toxins
Volume5
Issue number3
StatePublished - Oct 1 1996

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