Cadmium modulates diabetes-induced alterations in murine neuromuscular junction

Skeletal muscle function is compromised in diabetes mellitus and exposure to heavy metals may further complicate neuromuscular impairments. The present study investigated the effects of cadmium on diabetes induced dorsiflexor muscle dysfunction in C57 BL adult male mice. Forty mice were divided randomly into 2 groups (n=20 each). One group served as control and the other was injected once with i.p. streptozotocin (STZ) solution (60 mg/kg) to induce experimental diabetes. Each group was then divided into two sub-groups (n=10) of which one received 5 mM cadmium. Utilizing intracellular recording method, resting membrane potential (RMP) and miniature endplate potentials (MEPPs) were measured in dorsiflexor muscle obtained from urethane-anaesthetized (2 mg/g, i.p.) four weeks diabetic and matched control mice. Comparative analyses of isometric contractile characteristics of in situ dorsiflexor muscle were also conducted in both groups. In control mice, flexor muscle exposure to 5 mM cadmium for 10 min resulted in significant reduction in MEPPs frequencies and isometric twitch tensions without affecting RMP. In STZ-diabetic mice, the same exposure did not modify resting membrane potential and further decreased MEPPs frequencies and isometric twitch tensions. Current results indicated that cadmium probably via a Ca²⁺ antagonist and chelating activity at nerve terminals exacerbates diabetes complications.