Modulation of Ca by agents affecting voltage-sensitive Ca channels in mesangial cells.
The purpose of this study was to investigate the effects of depolarizing media and of Ca-channel activators and blockers on cytosolic free Ca in cultured rat mesangial cells. Membrane depolarizing media, containing 10-100 mM K+, dose dependently increased cytosolic Ca, and this effect was sustained and reversible. Nifedipine and lanthanum ion inhibited this increase, whereas verapamil was ineffective. A Ca-channel activator, BAY K 8644, dose dependently increased resting Ca levels, and nifedipine inhibited this effect. Moreover, the increase of Ca induced by maximally effective high K+ and BAY K 8644 was additive, suggesting differential mechanisms of action for the two channel activators. Nifedipine and verapamil decreased resting Ca levels by up to 35-40%. The results support the idea that mesangial cells have spontaneously active Ca channels that can be further activated by membrane depolarization or by the Ca-channel activator, BAY K 8644, and inhibited by the Ca-channel blockers, nifedipine or verapamil. Voltage-sensitive Ca channels in mesangial cells may play a role in the regulation of the glomerular filtration rate.
Yu
Y M
YM
Department of Pharmacology, University of Tennessee, Memphis 38163.
Lermioglu
F
F
Hassid
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005920:Glomerular Mesangium / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D007811:Lanthanum / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials; D009543:Nifedipine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013050:Spectrometry, Fluorescence; D014700:Verapamil / Q000494:pharmacology*
D015220:Calcium Channels; D007811:Lanthanum; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D014700:Verapamil; D009543:Nifedipine; D011188:Potassium; D002118:Calcium