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Norepinephrine reduces ω-conotoxin-sensitive Ca2+ currents in renal afferent neurons in rats.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2012 Feb 01; Vol. 302 (3), pp. F350-7. Date of Electronic Publication: 2011 Nov 02. - Publication Year :
- 2012
-
Abstract
- 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 (Ditting T, Tiegs G, Rodionova K, Reeh PW, Neuhuber W, Freisinger W, Veelken R. Am J Physiol Renal Physiol 297: F1427-F1434, 2009; Veelken R, Vogel EM, Hilgers K, Amman K, Hartner A, Sass G, Neuhuber W, Tiegs G. J Am Soc Nephrol 19: 1371-1378, 2008). However, it is not known whether renal afferent nerves are influenced by sympathetic nerve activity. We tested the hypothesis that norepinephrine (NE) influences voltage-gated Ca(2+) 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 (-100 to +80 mV, 300 ms, every 20 s). NE and appropriate adrenergic receptor antagonists were administered by microperfusion. NE (20 μM) reduced VGCC-mediated currents by 10.4 ± 3.0% (P < 0.01). This reduction was abolished by the α-adrenoreceptor inhibitor phentolamine and the α(2)-adrenoceptor antagonist yohimbine. The β-adrenoreceptor antagonist propranolol and the α(1)-adrenoceptor antagonist prazosin had no effect. The inhibitory effect of NE was abolished when N-type currents were blocked by ω-conotoxin GVIA, but was unaffected by other specific Ca(2+) channel inhibitors (ω-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(2+) channels via an α(2)-adrenoceptor-dependent mechanism. However, the exact site and the functional role of this interaction remains to be elucidated.
- Subjects :
- Adrenergic alpha-2 Receptor Antagonists pharmacology
Animals
Calcium Channel Blockers pharmacology
Cells, Cultured
Drug Interactions
Ganglia, Spinal cytology
Ganglia, Spinal physiology
Male
Neurons, Afferent cytology
Neurons, Afferent drug effects
Organ Culture Techniques
Patch-Clamp Techniques
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, alpha-2 physiology
Sympathetic Fibers, Postganglionic drug effects
Sympathetic Fibers, Postganglionic physiology
Yohimbine pharmacology
Calcium Channels physiology
Kidney innervation
Neurons, Afferent physiology
Norepinephrine pharmacology
omega-Conotoxins pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1466
- Volume :
- 302
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 22049399
- Full Text :
- https://doi.org/10.1152/ajprenal.00681.2010