Epithelial Ca2+ channels sensitive to dihydropyridines and activated by hyperpolarizing voltages.
Parathyroid hormone (PTH) increases transcellular Ca2+ absorption in renal cortical thick ascending limbs and distal convoluted tubules (DCT). In cells isolated from these nephron segments, PTH increases Ca2+ uptake by a pathway that is sensitive to dihydropyridine-type agonists and antagonists (B. J. Bacskai and P. A. Friedman. Nature Lond. 347: 388-391, 1990). Patch-clamp techniques were used to identify Ca(2+)-permeable channels in DCT cells. Channel activity was detectable in cell-attached patches only in cells pretreated with PTH. Ca2+ channels exhibited prolonged open times (seconds), had a low single-channel conductance (2.1 pS), and open channel probability increased at hyperpolarizing voltages (-50 to -90 mV). Channel activity was sensitive to dihydropyridine-type compounds, nifedipine, and BAY K8644, as was Ca2+ uptake. However, Ca2+ entry was insensitive to verapamil or omega-conotoxin. These results demonstrate that these channels mediate PTH-stimulated apical membrane Ca2+ entry in DCT cells, which are the principal Ca(2+)-transporting cells of the kidney.
Matsunaga
H
H
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755.
Stanton
B A
BA
Gesek
F A
FA
Friedman
P A
PA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D010281:Parathyroid Hormone / Q000494:pharmacology
D015220:Calcium Channels; D004095:Dihydropyridines; D010281:Parathyroid Hormone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester