Epithelial Ca2+ channels sensitive to dihydropyridines and activated by hyperpolarizing voltages

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Abstract
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.