Sensory Neurons With Afferents From Hind Limbs

Abstract

Sensory nerve fibers from the dorsal root ganglia (DRG) may contribute to the regulation of peripheral vascular resistance. Axons of DRG neurons of the lower thoracic cord project mainly to resistance vessels in the lower limbs, likely opposing the vasoconstrictor effects of the sympathetic activity. This mechanism might be of importance in hypertension with increased sympathetic activity. We tested the hypothesis that sensory neurons of the DRG in the lower thoracic cord show an altered sensitivity to mechanical stimuli in hypertension. Neurons from DRG (T11 to L1) of rats with hypertension (2 kidney-1 clip hypertensive rats and 5 of 6 nephrectomized rats) were cultured on coverslips. Current time relationships were established with whole-cell patch recordings. Cells were characterized under control conditions and after exposure to hypoosmotic solutions to induce mechanical stress. Neurons with projections to the kidney were studied for comparison. The hypoosmotic extracellular medium induced a significant change in conductance of the cells in all of the groups of rats. In hypertensive rats, responses of cells with hindlimb axons were significantly different from controls: (2 kidney-1 clip hypertensives: delta-351+/-52 pA and 5 of 6 nephrectomized rats: delta-372+/-43 pA versus controls: delta-190+/-25 pA; P<0.05). Responses of DRG cells with renal afferents to mechanical stress were unaffected. Neurons from DRG in the lower thoracic cord with projections to the lower limbs exhibited an increased sensitivity to mechanical stress. We speculate that this observation may indicate an increased activity of these neurons, their axons, and neurotransmitters in the control of resistance vessels in hypertension.

Sensory renal innervation: a kidney-specific firing activity due to a unique expression pattern of voltage-gated sodium channels?

“…Small flank incisions through skin and muscles were necessary to expose renal poles. The lipophilic tracer was transported retrogradely along the nerves to the cell bodies; 6 days later animals were euthanized and the neurons were harvested from DRG T 11-L2 (19,28).…”

“…Male Sprague-Dawley rats were anesthetized with isoflurane and euthanized by decapitation, and DRGs from T 11-L2 were dissected. Primary cultures of DRG neurons were obtained by mechanical and enzymatic dissociation as described previously (28). The ganglia were incubated with collagenase IA [2 mg/ml C9891 (Sigma-Aldrich, Munich, Germany) in DMEM (PAA Laboratories, Linz, Austria)] for 1 h in a 5% CO2 incubator at 37°C.…”

“…A laser beam (532 nm) was mounted to the patch-clamp setup to detect DiI-positive, renal DRG cells by fluorescence. From previous experiments, we knew that the nonrenal neurons in the DRGs mostly have axonal input from the hindlimbs (28).…”

“…We described earlier that renal afferent neurons, situated in the DRG Th 11 -L 2 , exhibited a specific response to acidic stimulation compared with nonrenal neurons with projections mostly from the lower limb (19,20,28). Interestingly, neurons with projections to the kidney seemed to show a significant different reaction upon changes in membrane potential.…”

“…One possible explanation for this fact is the difficult access to the afferent sensory nerve endings situated in the kidney as well as the demanding task to record afferent activity in multifiber preparations of renal nerves containing a high number of actively firing sympathetic units. On the other hand, the cell body of the first neuron of the afferent innervation is situated in the dorsal root ganglion (DRG) and therefore accessible for cell culture and electrophysiological investigation (28).…”