Article
Acid Sensitive Currents in Renal Afferent Nerve Fibers with Vanilloid Receptors
Ph abhängige Ströme in afferenten Nervenfasern der Niere
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Published: | August 8, 2006 |
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Chemosensitive afferent nerve fibers from the kidneys are putatively involved in the upregulation of sympathetic nerve activity in hypertension and accompanying renal disease. It is unknown in how far acid sensitive ion channels dependent on vanilloid receptor (VR1) activation are of importance in the stimulation of these afferent pathways [1. neuron - dorsal root ganglion neurones (DRGs)] like in other organ systems.
Hence, primary cultures of retrogradely labeled DRGs with renal axons from Sprague Dawley rats and VR1 knockout mice were investigated by whole-cell patch-clamping. Transient and sustained currents could be induced by microperfusion with solutions of pH6 and pH5. Sensitizing effects of the inflammatory mediator bradykinin (BK) were investigated by preadministration of this drug to the cells (1µM). Renal DRGs showed significantly higher amplitudes of acid induced transient and sustained currents than non-renal cells in rats; transient: (15.99 ± 5.05 pA/pF vs 0.36 ± 0.17* pA/pF, mean ± SEM at pH 6) sustained: (3.67 ± 1.13 pA/pF vs 0.64 ± 0.14* pA/pF at pH 6 and 20,04 ± 4,51 pA/pF vs 6,22 ± 1,18* pA/pF at pH 5) (* p < 0.05). BK increased slightly but significantly sustained currents at pH 6 but not at pH 5 in renal and non-renal cells. The putative VR1 receptor antagonist Capsazepin in respective doses significantly blunted by up to50% the sustained responses to acidic solutions as compared to a group of neurons without pretreatment. In VR1 receptor knock-out mice the sustained response to acidic solutions was completely abolished, but the transient response was unaltered as compared to respective controls.
Proton-induced sustained currents of renal afferents are likely vanilloid receptor dependant in rats and mice They are sensitized by inflammatory mediators as BK. They might contribute to increased sympathetic nerve activity in hypertension and hypertensive nephropathy