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 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 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⁺/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.