Failure of nimodipine to prevent or correct the long-term nerve conduction defect and increased neuronal Ca(2+)-currents in the diabetic BB/W-rat.
It has been suggested that L-type Ca2+ channel antagonists exert a beneficial effect on nerve conduction velocity (NCV) slowing in short-term experimental diabetic neuropathy. We examined the effects of long-term treatment with the L-channel blocker, nimodipine, on two aspects of neuronal function previously documented to be abnormal in the spontaneously diabetic BB/W-rat: nerve conduction velocity and calcium influx in dorsal root ganglion (DRG) neurons. Treatment with 20 mg/kg nimodipine i.p. every 48 h from onset of diabetes for 6 months led to a transient, non-significant (30%) improvement in NCV. Intervention with the same regimen from 3 to 6 months of diabetes had no corrective effect on the already established NCV defect. Voltage activated calcium currents were recorded in isolated DRG neurons from nimodipine-treated and untreated diabetic and non-diabetic age-matched BB/W control rats. The peak high-threshold calcium current density (IDCa, pA/pF) was significantly larger in non-treated diabetic rats compared with control rats (157 +/- 12 vs. 66 +/- 5.5 (P < or = 0.05)). Long-term treatment with nimodipine was associated with a non-significant (28%) decrease (112 +/- 29) in the IDCa compared with non-treated diabetic rats. We conclude that L-channel mediated perturbations of cytosolic Ca2+ levels are only of minor pathophysiologic significance in the development of chronic diabetic neuropathy.
Ristic
H
H
Department of Pathology, University of Michigan, Ann Arbon 48103, USA.
Wiley
J W
JW
Hall
K E
KE
Sima
A A
AA
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D015331:Cohort Studies; D003929:Diabetic Neuropathies / Q000188:drug therapy; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D006442:Glycated Hemoglobin / Q000032:analysis; D008297:Male; D009431:Neural Conduction / Q000187:drug effects* / Q000502:physiology; D009553:Nimodipine / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011913:Rats, Inbred BB; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology
D001786:Blood Glucose; D002118:Calcium; D002121:Calcium Channel Blockers; D006442:Glycated Hemoglobin; D009553:Nimodipine