T-type Ca2+ channels are required for adrenocorticotropin-stimulated cortisol production by bovine adrenal zona fasciculata cells

Mol Endocrinol. 1993 Aug;7(8):1031-40. doi: 10.1210/mend.7.8.8232302.


The function of low voltage-activated T-type Ca2+ channels in ACTH-stimulated cortisol production by bovine adrenal zona fasciculata cells (AZF) was explored in patch clamp and secretion studies. Nearly all AZF cells expressed only a low voltage-activated T-type Ca2+ current (IT) that was blocked by the diphenylbutylpiperidine (DPBP) Ca2+ antagonists penfluridol and pimozide with IC50S of 0.3 and 0.5 microM, respectively. Dihydropyridine (DHP) Ca2+ antagonists, including nimodipine, nisoldipine, and felodipine, also blocked T-type Ca2+ current with IC50S ranging from 3.5-8.8 microM. Inhibition of IT by DPBP and DHP antagonists was voltage and use dependent. ACTH (1 nM) stimulated large (> 50-fold) increases in cortisol production by AZF cells, which were inhibited by Ca2+ antagonists at concentrations similar to those which blocked IT. Inhibition of cortisol production by Ca2+ antagonists was specific; ACTH-induced insulin-like growth factor-I production by AZF cells was not affected by DPBP antagonists. The L channel-specific DHP Ca2+ agonist (-)Bay K 8644 did not enhance basal or ACTH-stimulated cortisol synthesis. These results demonstrate that functional T-rather than L-type Ca2+ channels are required for ACTH-stimulated cortisol synthesis. They also suggest that these low voltage-activated channels, acting as the primary pathway for Ca2+ entry into AZF cells, couple ACTH-stimulated membrane depolarization to steroid hormone production.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenocorticotropic Hormone / pharmacology*
  • Animals
  • Calcium / physiology*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / classification
  • Calcium Channels / physiology*
  • Cattle
  • Cells, Cultured
  • Cyclic AMP / physiology
  • Dihydropyridines / pharmacology
  • Hydrocortisone / biosynthesis*
  • Hydrocortisone / metabolism
  • Insulin-Like Growth Factor I / biosynthesis
  • Male
  • Penfluridol / pharmacology
  • Pimozide / pharmacology
  • Signal Transduction
  • Zona Fasciculata / drug effects*
  • Zona Fasciculata / metabolism


  • Calcium Channel Blockers
  • Calcium Channels
  • Dihydropyridines
  • Pimozide
  • Penfluridol
  • Insulin-Like Growth Factor I
  • 1,4-dihydropyridine
  • Adrenocorticotropic Hormone
  • Cyclic AMP
  • Calcium
  • Hydrocortisone