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

Aim: In rat afferent arterioles we investigated the role of Na + entry in noradrenaline (NA)-induced depolarization and voltage-dependent Ca 2+ entry together with the importance of the transient receptor potential channel (TRPC) subfamily for non-voltage-dependent Ca 2+ entry. Methods: R 340/380 Fura-2 fluorescence was used as an index for intracellular free Ca 2+ concentration ([Ca 2+ ] 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 R 340/380 (control response 123%). However, as the R 340/380 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 + /Ca 2+ 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 Gd 3+ (100 μM) further reduced the plateau Ca 2+ 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 Ca 2+ entry via L-type channels. In addition, the results are consistent with the idea that TRPC1/3/6 Ca 2+ -permeable cation channels expressed in afferent arteriolar smooth muscle cells mediate Ca 2+ entry during NA stimulation.