Triethyltin intoxication alters acetylcholine release from rat phrenic nerve-hemidiaphragm

Triethyltin (TET) exposure produces, among other symptoms, muscular weakness . The etiology of this phenomenon is obscure, but the symptoms suggest impaired cholinergic transmission at the neuromuscular junction. Therefore, acetylcholine (ACh) release was assessed in the vascularly perfused phrenic nerve-hemidiaphragm isolated from rats subjected to acute or chronic in vivo exposure to TET. Adult male hooded Long-Evans rats (250-350 grams) were exposed acutely to one injection of TET (10 mg/kg IP), or chronically to TET (30 mg/L) in their drinking water. Hemidiaphragms were obtained from treated and age-matched control rats 24 hours after acute exposure or one, two, or three weeks after initiation of the chronic exposure regimen. ACh release was assessed during unstimulated (spontaneous), stimulated (7 Hz), and supra-stimulated (20 Hz) conditions. Ach release was not altered in the hemidiaphragms of acutely exposed rats. Rats chronically exposed to TET showed normal spontaneous release, a trend towards decreased stimulated (7 Hz) release, and an almost complete failure to release Ach in response to 20 Hz stimulation. The data are discussed with respect to known TET effects on cellular bioenergetics and the consequences for neurotransmitter synthesis and release mechanisms.