Norepinephrine reduces ω-conotoxin-sensitive Ca2+ currents in renal afferent neurons in rats

Tilmann Ditting, Peter Linz, Wolfgang Freisinger, Sonja Heinlein, Peter W. Reeh, Christian Fiedler, Kirsten Siegel, Karie E. Scrogin, Winfried Neuhuber, Roland Veelken
2012 AJP - Renal Physiology  
Ditting T, Linz P, Freisinger W, Heinlein S, Reeh PW, Fiedler C, Siegel K, Scrogin KE, Neuhuber W, Veelken R. Norepinephrine reduces -conotoxin-sensitive Ca 2ϩ currents in renal afferent neurons in rats. Sympathetic efferent and peptidergic afferent renal nerves likely influence hypertensive and inflammatory kidney disease. Our recent investigation with confocal microscopy revealed that in the kidney sympathetic nerve endings are colocalized with afferent nerve fibers not known whether renal
more » ... erent nerves are influenced by sympathetic nerve activity. We tested the hypothesis that norepinephrine (NE) influences voltage-gated Ca 2ϩ channel currents in cultured renal dorsal root ganglion (DRG) neurons, i.e., the first-order neuron of the renal afferent pathway. DRG neurons (T11-L2) retrogradely labeled from the kidney and subsequently cultured, were investigated by whole-cell patch clamp. Voltage-gated calcium channels (VGCC) were investigated by voltage ramps (Ϫ100 to ϩ80 mV, 300 ms, every 20 s). NE and appropriate adrenergic receptor antagonists were administered by microperfusion. NE (20 M) reduced VGCC-mediated currents by 10.4 Ϯ 3.0% (P Ͻ 0.01). This reduction was abolished by the ␣-adrenoreceptor inhibitor phentolamine and the ␣ 2-adrenoceptor antagonist yohimbine. The ␤-adrenoreceptor antagonist propranolol and the ␣ 1-adrenoceptor antagonist prazosin had no effect. The inhibitory effect of NE was abolished when N-type currents were blocked by -conotoxin GVIA, but was unaffected by other specific Ca 2ϩ channel inhibitors (-agatoxin IVA; nimodipine). Confocal microscopy revealed sympathetic innervation of DRGs and confirmed colocalization of afferent and efferent fibers within in the kidney. Hence NE released from intrarenal sympathetic nerve endings, or sympathetic fibers within the DRGs, or even circulating catecholamines, may influence the activity of peptidergic afferent nerve fibers through N-type Ca 2ϩ channels via an ␣2-adrenoceptordependent mechanism. However, the exact site and the functional role of this interaction remains to be elucidated. dorsal root ganglion; renal afferent neuron; ␣ 2-adrenoreceptor; voltage-gated Ca 2ϩ channel; VGCC; -agatoxin
doi:10.1152/ajprenal.00681.2010 pmid:22049399 fatcat:effykyeauzfqjf64lbgx64osve