Parathyroid cells express dihydropyridine-sensitive cation currents and L-type calcium channel subunits.
Parathyroid cells express Ca2+ -conducting currents that are activated by raising the extracellular Ca2+ concentration ([Ca2+]o). We investigated the sensitivity of these currents to dihydropyridines, the expression of voltage-dependent Ca(2+) channel (VDCC) subunits, and the effects of dihydropyridines on the intracellular free [Ca2+] ([Ca2+]i) and secretion in these cells. Dihydropyridine channel antagonists dose dependently suppressed Ca2+ -conducting currents, and agonists partially reversed the inhibitory effects of the antagonists in these cells. From a bovine parathyroid cDNA library, we isolated cDNA fragments encoding parts of an alpha(1S)- and a beta(3)-subunit of L-type Ca(2+) channels. The alpha(1S)-subunit cDNA from the parathyroid represents an alternatively spliced variant lacking exon 29 of the corresponding gene. Northern blot analysis and immunocytochemistry confirmed the presence of transcripts and proteins for alpha(1)- and beta(3)-subunits in the parathyroid gland. The addition of dihydropyridines had no significant effects on high [Ca2+]o-induced changes in [Ca2+]i and parathyroid hormone (PTH) release. Thus our studies indicate that parathyroid cells express alternatively spliced L-type Ca2+ channel subunits, which do not modulate acute intracellular Ca2+ responses or changes in PTH release.
Chang
W
W
Endocrine Research Unit, Department of Medicine, Veterans Affairs Medical Center, University of California, San Francisco, California 04121, USA.
Pratt
S A
SA
Chen
T H
TH
Tu
C L
CL
Mikala
G
G
Schwartz
A
A
Shoback
D
D
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002118:Calcium / Q000494:pharmacology; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002417:Cattle; D002469:Cell Separation; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008969:Molecular Sequence Data; D010280:Parathyroid Glands / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000096:biosynthesis / Q000235:genetics; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D007473:Ion Channels; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004247:DNA; D002118:Calcium