PARATHYROID HORMONE-ACTIVATED CALCIUM CHANNELS IN AN OSTEOBLAST-LIKE CLONAL OSTEOSARCOMA CELL-LINE - CAMP-DEPENDENT AND CAMP-INDEPENDENT CALCIUM CHANNELS

  • 5 June 1987
    • journal article
    • research article
    • Vol. 262  (16) , 7711-7718
Abstract
Changes in free cytosolic calcium were measured in LMR-106 cells in response to parathyroid hormone (PTH) stimulation. Bovine PTH-(1-34) induced an increase in [Ca2+]i with the contour of the rise in [Ca2+]i occurring in three successive phases: 1) a rapid increase in [Ca2+]i occurring within seconds, 2) rapid decrement in [Ca2+]i to near-resting levels within 1 min, and 3) slow increment in [Ca2+]i. Phase one and phase three increases in [Ca2+]i were dependent on medium calcium. The phase one rise in [Ca2+]i was inhibitable by the calcium channel blockers lanthanum and verapamil. Only the phase one rise in [Ca2+]i was blocked by preincubation of the cells with the phorbol ester, phorbol 12-myristate 13-acetate. This channel was also blocked when cellular cAMP levels were increased prior to PTH stimulation. The phase two decrement of [Ca2+]i was due to the rapid inactivation of the phase one calcium channel. The phase three rise in [Ca2+]i was mediated by cellular cAMP levels. This cAMP-dependent Ca2+ channel was insensitive to pretreamtent of the cells with phorbol diesters and showed low sensitivity to Ca2+ channel blockers. It is concluded that UMR-106 cells respond to PTH stimulation by the activation of a cAMP-independent Ca2+ channel. This channel rapidly inactivates. The subsequent PTH-dependent increase in cellular cAMP is followed by activation of a cAMP-dependent Ca2+channel resulting in a slow rise in [Ca2+]i.