Depolarization affects neuromuscular junction of streptozotocin-diabetic mice

The effect of increasing extracellular calcium concentration on spontaneous transmitter release was studied at both soleus (slow) and fast extensor di gitorum longus (EDL) nerve terminals of control and streptozotocin-induced diabetic (STZ-D) young C57 BL mice (7 months old) depolarized by high (20 m M) extracellular potassium [K](o). Diabetes was induced by i.p. injection w ith a single dose of streptozotocin (200 mg/kg) at the age 5 months and the electrophysiological studies were carried out after 8 more weeks. By using intracellular recording, miniature endplate potentials (MEPPs) were first recorded in a normal [K](o) Krebs solution. Subsequently, MEPPs were record ed in high [K](o) Krebs solution with 4 different Ca concentrations: Ca-fre e/ethylene glycol-bis (beta-aminoethyl either)-N,N,N',N'-tetra acetic acid (EGTA), 0.5, 1.5 and 2 mM Ca. MEPP frequency was lower at STZ-D than contro l nerve terminals in EDL but not soleus. However, MEPP frequency was progre ssively higher at both EDL and soleus of STZ-D than control with increasing Ca concentration in Krebs that contained 20 mM [K](o). In STZ-D slow soleu s muscle, depolarization produced 0.7, 4.3, 41.6 and 62.7 vs 1.4, 2.8, 20.7 and 31.6 Hz for control in the 4 different Ca concentrations. In STZ-D fas t EDL muscle, depolarization produced 0.5, 4.9, 48.2 and 66.8 vs 1.2, 2.5, 27 and 35.4 Hz for control in the 4 different Ca concentrations. Bimodal an d unimodal MEPP amplitude were present at both slow and fast nerve terminal s. However, depolarization increased the percentage of bimodal MEPP amplitu de in STZ-D compared to control (p<0.01) mice in EDL but not soleus. The re sults revealed that these changes in muscle firing pattern may provide a pr otective effect against diabetes-induced neuropathy at the neuromuscular ju nction.