Voltage‐dependent calcium currents are enhanced in dorsal root ganglion neurones from the Bio Bred/Worchester diabetic rat.

1. Whole‐cell, high‐threshold, voltage‐dependent calcium currents (ICa) were enhanced in acutely dissociated, capsaicin‐sensitive dorsal root ganglion neurones from diabetic Bio Bred/Worchester (BB/W) rats, compared with those from age‐matched, non‐diabetic controls. The magnitude of the enhancement increased with the duration of diabetes, and reached significance at diabetic durations of 6 months (diabetic: 6.3 +/‐ 0.4 nA; current density (CD), 157 +/‐ 12 pA pF‐1; means +/‐ S.E.M., n = 9, P < 0.01; control: 3.9 +/‐ 0.6 nA; CD, 116 +/‐ 11 pA pF‐1; n = 18) and 8 months (diabetic: 7.6 +/‐ 0.4 nA; CD, 177 +/‐ 25 pA pF‐1; n = 11, P < 0.005; control: 5.1 +/‐ 0.5 nA; CD, 111 +/‐ 26 pA pF‐1; n = 15). Low‐threshold, voltage‐dependent ICa were also enhanced in neurones from animals diabetic for 8 months (diabetic: 2.5 +/‐ 0.7 nA, n = 4, P < 0.05; control: 0.7 +/‐ 0.5 nA, n = 6). 2. The ICa enhancement was prevented by long‐term treatment of diabetic animals with an aldose reductase inhibitor (ARI; peak ICa at 6 months: 4.41 +/‐ 0.48 nA, n = 2; at 8 months: 4.32 +/‐ 0.60 nA, n = 9). 3. The ICa enhancement was not due to a shift in the voltage dependence of either the current‐voltage relationship or steady‐state inactivation. 4. The L channel antagonist nifedipine and preferential N channel antagonist omega‐conotoxin GVIA (omega‐CgTX) caused a greater inhibition of high‐threshold ICa in diabetic neurones compared with controls (nifedipine: control: 25 +/‐ 3%, n = 26; diabetic: 36 +/‐ 7%, n = 11; omega‐CgTX: control: 40 +/‐ 4%, n = 21; diabetic: 50 +/‐ 7%, n = 7). Diabetic neurones also demonstrated a significantly greater residual current (2.44 +/‐ 0.34 nA, n = 7) in the presence of both antagonists vs. controls (1.28 +/‐ 0.30 nA, n = 8, P < 0.05), suggesting that N‐, L‐ and additional non‐N‐, non‐L‐type high‐threshold ICa were enhanced.