Calcium channel blocker influences the density of alpha-actinin labeling at the rat neuromuscular junction.
Alpha-actinin is a muscle protein located along the Z-disc. Incubation of frog muscle with the calcium ionophore, A23187, can decrease the immunogold labelling of alpha-actinin. Pyridostigmine (PYR) is an inhibitor of acetylcholinesterase, which causes disruption of Z-discs only in the region of the motor endplate. This is probably due to excess influx of calcium ions, leading to activation of proteases. Pretreating animals with the calcium channel blocker diltiazem can significantly reduce damage to the Z-discs at the motor endplate caused by PYR. It was of interest to determine whether the distribution of alpha-actinin had been altered following PYR administration and whether diltiazem could prevent those changes. There was less alpha-actinin labelling at the motor endplate compared to away from this region for all treatment groups. Animals administered diltiazem showed less labelling compared to PYR, but with no disruption of Z-discs at the motor endplate following diltiazem. Pretreatment with diltiazem reduced the incidence of Z-disc damage, but the degree of alpha-actinin labeling at the endplate was less than that seen with diltiazem alone. The greater effect seen at the endplate implies that neuromuscular activity is an important factor. The drugs may be causing a reduction in alpha-actinin labelling by different mechanisms.
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CK
Veterans Administration Medical Center, Neurocytology Lab, Portland, OR 97201.
Kriho
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Kriho
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Hopkins
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Matsumura
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Pappas
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GD
D000185:Actinin / Q000032:analysis* / Q000187:drug effects; D000818:Animals; D004110:Diltiazem / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009045:Motor Endplate / Q000187:drug effects / Q000378:metabolism; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000185:Actinin; D004110:Diltiazem; D011729:Pyridostigmine Bromide