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 digitorum longus (EDL) nerve terminals of control and streptozotocin-induced diabetic (STZ-D) young C57 BL mice (7 months old) depolarized by high (20 mM) extracellular potassium [K]o. Diabetes was induced by i.p. injection with 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 recorded in high [K]o Krebs solution with 4 different Ca concentrations: Ca-free/ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetra acetic acid (EGTA), 0.5, 1.5 and 2 mM Ca. MEPP frequency was lower at STZ-D than control nerve terminals in EDL but not soleus. However, MEPP frequency was progressively 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 soleus 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 fast 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 and unimodal MEPP amplitude were present at both slow and fast nerve terminals. However, depolarization increased the percentage of bimodal MEPP amplitude in STZ-D compared to control (p<0.01) mice in EDL but not soleus. The results revealed that these changes in muscle firing pattern may provide a protective effect against diabetes-induced neuropathy at the neuromuscular junction.
Fahim
M A
MA
Department of Physiology, Faculty of Medicine, U.A.E. University, Al Ain, United Arab Emirates. m.fahim@uaeu.ac.ae
Al Shuaib
W
W
Davidson
N
N
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016764:Cell Polarity; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000503:physiopathology; D009469:Neuromuscular Junction / Q000503:physiopathology*; D013311:Streptozocin
D013311:Streptozocin; D000109:Acetylcholine; D002118:Calcium