Selective T-Type Calcium Channel Blockade Alleviates Hyperalgesia in ob/ob Mice

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FIG. 3.
FIG. 3.

Upregulation of T-current in smaller DRG cells after the development of hyperglycemia in ob/ob mice. A: qRT-PCR analysis of the relative expression of mRNA for three isoforms of T-channels in lumbar DRGs and from ob/ob mice and age-matched wild-type controls at 10–12 weeks of age. There was a fourfold upregulation of α1H isoform but no significant change in α1G and α1I isoforms in lumbar DRG tissues from ob/ob mice compared with wild-type mice (*P < 0.001). B: Raw current traces evoked in DRG cells from wild-type (top panel) and ob/ob (bottom panel) mice 10–12 weeks old by voltage steps from −90 mV (Vh [holding potential]) to Vt (test potential) from −60 through −20 mV in 10-mV increments. Calibrations on top bars pertain to both panels. Ob/ob mouse had increased absolute amplitude of isolated T-current more than twofold at a range of test potentials from −50 to −20 mV. C: Histograms indicate average T-current amplitudes (Vt −30 mV) in DRG cells from wild-type (open bars) and ob/ob mice (filled bars) expressed as percent current density normalized to wild type. The size of each sample is in parentheses; vertical bars are SE of multiple determinations. Weeks of age for each of the five groups are indicated at the bottom. In each group, recordings were made from at least three mice. At the peak of hyperglycemia and sensory hypersensitivity (age 10–12 weeks), peak T-current density averaged 20 ± 4 pA/pF in the wild-type group and 44 ± 7 pA/pF in the ob/ob group. At 16 weeks of age, T-currents were still significantly upregulated in the ob/ob group by about 1.5-fold, with normalization occurring at 18 weeks of age. Before the onset (5–6 weeks) and at the outset of hyperglycemia (28–30 weeks of age), peak T-current density was not different between the wild-type group and the ob/ob group (P > 0.05). Asterisk indicates significant value by Mann-Whitney test (P < 0.01); n.s. indicates P > 0.05. HPRT, hypoxanthine-guanine-phosphoribosyltransferase; WT, wild type.

This Article

  1. Diabetes vol. 58 no. 11 2656-2665