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


CONCLUSIONS
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.
Salomonsson
M
M
Division of Renal and Vascular Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. maxsalomon@mfi.ku.dk
Braunstein
T H
TH
Holstein-Rathlou
N-H
NH
Jensen
L J
LJ
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism; D001593:Benzyl Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005682:Gadolinium / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D050052:TRPC Cation Channels / Q000187:drug effects* / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D013997:Time Factors
C487681:2-(4-(4-nitrobenzyloxy)benzyl)thiazolidine-4-carboxylic acid ethyl ester; D000322:Adrenergic Agonists; D001593:Benzyl Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007093:Imidazoles; D019831:Sodium-Calcium Exchanger; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D053778:Thiazolidines; C492145:Trpc6 protein, rat; C096351:transient receptor potential cation channel, subfamily C, member 1; D012964:Sodium; D005682:Gadolinium; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine