Na+‐independent, nifedipine‐resistant rat afferent arteriolar Ca2+ responses to noradrenaline: possible role of TRPC channels

M Salomonsson, TH Braunstein… - Acta …, 2010 - Wiley Online Library
Acta physiologica, 2010Wiley Online Library
Aim: In rat afferent arterioles we investigated the role of Na+ entry in noradrenaline (NA)‐
induced depolarization and voltage‐dependent Ca2+ entry together with the importance of
the transient receptor potential channel (TRPC) subfamily for non‐voltage‐dependent Ca2+
entry. Methods: R 340/380 Fura‐2 fluorescence was used as an index for intracellular free
Ca2+ concentration ([Ca2+] i). Immunofluorescence detected the expression of TRPC
channels. Results: TRPC 1, 3 and 6 were expressed in afferent arteriolar vascular smooth …
Abstract
Aim:  In rat afferent arterioles we investigated the role of Na+ entry in noradrenaline (NA)‐induced depolarization and voltage‐dependent Ca2+ entry together with the importance of the transient receptor potential channel (TRPC) subfamily for non‐voltage‐dependent Ca2+ entry.
Methods:  R 340/380 Fura‐2 fluorescence was used as an index for intracellular free Ca2+ concentration ([Ca2+]i). Immunofluorescence detected the expression of TRPC channels.
Results:  TRPC 1, 3 and 6 were expressed in afferent arteriolar vascular smooth muscle cells. Under extracellular Na+‐free (0 Na) conditions, the plateau response to NA was 115% of the baseline R340/380 (control response 123%). However, as the R340/380 baseline increased (7%) after 0 Na the plateau reached the same level as during control conditions. Similar responses were obtained after blockade of the Na+/Ca2+ exchanger. The L‐type blocker nifedipine reduced the plateau response to NA both under control (from 134% to 116% of baseline) and 0 Na conditions (from 112% to 103% of baseline). In the presence of nifedipine, the putative TRPC channel blockers SKF 96365 (30 μm) and Gd3+ (100 μm) further reduced the plateau Ca2+ responses to NA (from 117% to 102% and from 117% to 110% respectively).
Conclusion:  We found that Na+ is not crucial for the NA‐induced depolarization that mediates Ca2+ entry via L‐type channels. In addition, the results are consistent with the idea that TRPC1/3/6 Ca2+‐permeable cation channels expressed in afferent arteriolar smooth muscle cells mediate Ca2+ entry during NA stimulation.
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