Dihydropyridine- and voltage-sensitive Ca2+ entry in human parathyroid cells.
Patch-clamp and fluorescence measurements of cytoplasmic Ca(2+) concentration ([Ca(2+)](i)) were performed to directly detect extracellular Ca(2+) entry into cultured parathyroid cells from patients with secondary hyperparathyroidism. Cells loaded with fluo-3 AM or fluo-4 AM showed a transient increase in fluorescence (Ca(2+) transient) following 10 s exposure to 150 mm K(+) solution in the presence of millimolar concentrations of external Ca(2+). The Ca(2+) transient was completely inactivated after 30-40 s exposure to the high-K(+) solution, was reduced by dihydropyridine antagonists and was enhanced by FPL-64176, an L-type Ca(2+) channel agonist. The electrophysiological and pharmacological properties of the whole-cell Ca(2+) and Ba(2+) currents were similar to those of L-type Ca(2+) channels. The Ca(2+) transients induced by 10 s exposure to 3.0 mm extracellular Ca(2+) concentration ([Ca(2+)](o)) were inhibited by dihydropyridine antagonists and were partly inactivated following 30-40 s exposure to the high-K(+) solution. These results demonstrate, for the first time, that human parathyroid cells express L-type-like Ca(2+) channels that are possibly involved in the [Ca(2+)](o)-induced change in [Ca(2+)](i). This Ca(2+) entry system might provide a compensatory pathway for the negative feedback regulation of parathyroid hormone secretion, especially in hyperplastic conditions in which the Ca(2+)-sensing receptor is poorly expressed.
Department of Nephrology and Hypertension, The Jikei University School of Medicine, 3-25-8 Nishishinbashi, Minato-ku, Tokyo 105-8461, Japan. keitaro@mrj.biglobe.ne.jp
Keitaro
K
Yokoyama
Douchi
D
Matsuba
Satomi
S
Adachi-Akahane
Hiroshi
H
Takeyama
Isao
I
Tabei
Akifumi
A
Suzuki
Toshiaki
T
Shibasaki
Rinako
R
Iida
Ichiro
I
Ohkido
Tatsuo
T
Hosoya
Norio
N
Suda
D001464:Barium / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology*; D006801:Humans; D010280:Parathyroid Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D001464:Barium; C038806:1,4-dihydropyridine; D002118:Calcium