FAILURE OF NIMODIPINE TO PREVENT OR CORRECT THE LONG-TERM NERVE-CONDUCTION DEFECT AND INCREASED NEURONAL CA2-CURRENTS IN THE DIABETIC BB()W-RAT/

It has been suggested that L-type Ca2+ channel antagonists exert a ben eficial effect on nerve conduction velocity (NCV) slowing in short-ter m experimental diabetic neuropathy. We examined the effects of long-te rm treatment with the L-channel blocker, nimodipine, on two aspects of neuronal function previously documented to be abnormal in the spontan eously diabetic BB/W-rat: nerve conduction velocity and calcium influx in dorsal root ganglion (DRG) neurons. Treatment with 20 mg/kg nimodi pine i.p. every 48 h from onset of diabetes for 6 months led to a tran sient, 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 curre nts 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 (I-DCa, pA/pF) was signif icantly larger in non-treated diabetic rats compared with control rats (157 +/- 12 vs. 66 +/- 5.5 (P less than or equal to 0.05)). Long-term treatment with nimodipine was associated with a non-significant (28%) decrease (112 +/- 29) in the I-DCa 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 dev elopment of chronic diabetic neuropathy.