Reduction in voltage-gated K+ channel activity in primary sensory neurons in painful diabetic neuropathy: role of brain-derived neurotrophic factor.

Xue-Hong Cao, Hee-Sun Byun, Shao-Rui Chen, You-Qing Cai, Hui-Lin Pan

Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Journal of neurochemistry 2010 Sep 1

filter terms:

Abnormal hyperexcitability of primary sensory neurons plays an important role in neuropathic pain. Voltage-gated potassium (Kv) channels regulate neuronal excitability by affecting the resting membrane potential and influencing the repolarization and frequency of the action potential. In this study, we determined changes in Kv channels in dorsal root ganglion (DRG) neurons in a rat model of diabetic neuropathic pain. The densities of total Kv, A-type (IA) and sustained delayed (IK) currents were markedly reduced in medium- and large-, but not in small-, diameter DRG neurons in diabetic rats. Quantitative RT-PCR analysis revealed that the mRNA levels of IA subunits, including Kv1.4, Kv3.4, Kv4.2, and Kv4.3, in the DRG were reduced approximately 50% in diabetic rats compared with those in control rats. However, there were no significant differences in the mRNA levels of IK subunits (Kv1.1, Kv1.2, Kv2.1, and Kv2.2) in the DRG between the two groups. Incubation with brain-derived neurotrophic factor (BDNF) caused a large reduction in Kv currents, especially IA currents, in medium and large DRG neurons from control rats. Furthermore, the reductions in Kv currents and mRNA levels of IA subunits in diabetic rats were normalized by pre-treatment with anti-BDNF antibody or K252a, a TrkB tyrosine kinase inhibitor. In addition, the number of medium and large DRG neurons with BDNF immunoreactivity was greater in diabetic than control rats. Collectively, our findings suggest that diabetes primarily reduces Kv channel activity in medium and large DRG neurons. Increased BDNF activity in these neurons likely contributes to the reduction in Kv channel function through TrkB receptor stimulation in painful diabetic neuropathy.

Citation

Xue-Hong Cao, Hee-Sun Byun, Shao-Rui Chen, You-Qing Cai, Hui-Lin Pan. Reduction in voltage-gated K+ channel activity in primary sensory neurons in painful diabetic neuropathy: role of brain-derived neurotrophic factor. Journal of neurochemistry. 2010 Sep 1;114(5):1460-75