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Related Experiment Videos

Capacitative Ca2+ entry regulates Ca(2+)-sensitive adenylyl cyclases

D M Cooper1, M Yoshimura, Y Zhang

  • 1Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.

The Biochemical Journal
|February 1, 1994
PubMed
Summary
This summary is machine-generated.

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Calcium ions (Ca2+) can regulate adenylyl cyclase activity in cells. This study demonstrates that Ca2+ entry physiologically modulates adenylyl cyclase types I and VI in human cells, impacting cyclic AMP synthesis.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • Adenylyl cyclases are enzymes that synthesize cyclic AMP (cAMP).
  • Many adenylyl cyclase species show Ca2+ sensitivity in vitro.
  • Physiological relevance of Ca2+ regulation in intact cells is unclear due to confounding factors like G-protein subunits and protein kinase C activation.

Purpose of the Study:

  • To determine if physiological increases in intracellular Ca2+ regulate adenylyl cyclase activity in intact cells.
  • To investigate the specific effects of Ca2+ entry on adenylyl cyclase types I and VI.
  • To establish a reliable method for studying Ca2+ regulation of adenylyl cyclases independent of hormonal signaling pathways.

Main Methods:

  • Expression of human adenylyl cyclase types I and VI in human embryonic kidney 293 cells.

Related Experiment Videos

  • Induction of capacitative Ca2+ entry to elevate intracellular Ca2+ levels.
  • Measurement of cyclic AMP synthesis.
  • Use of lanthanum ions (La3+) to block Ca2+ entry.

    • Main Results:

    • Capacitative Ca2+ entry stimulated adenylyl cyclase type I activity.
    • Capacitative Ca2+ entry inhibited adenylyl cyclase type VI activity.
    • Blockade of Ca2+ entry with La3+ abolished these effects on cyclic AMP synthesis.

    Conclusions:

    • Adenylyl cyclases sensitive to Ca2+ in vitro can be physiologically regulated by Ca2+ entry in intact cells.
    • Adenylyl cyclase types I and VI exhibit distinct responses (stimulation and inhibition, respectively) to physiologically relevant Ca2+ influx.
    • These findings indicate that adenylyl cyclases are poised to respond to intracellular Ca2+ fluctuations in their native tissues.