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Related Experiment Videos

Postnatal decrease in muscarinic cholinergic influence on Ca2+ currents of rabbit ventricular cells

T Osaka1, R W Joyner, R Kumar

  • 1Todd Franklin Cardiac Research Laboratory, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322.

The American Journal of Physiology
|June 1, 1993
PubMed
Summary
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Muscarinic cholinergic modulation of L-type calcium current (ICa) decreases in rabbit ventricular cells after birth. This developmental change involves reduced inhibitory G protein influence on adenylyl cyclase activity, impacting cardiac function.

Area of Science:

  • Cardiology
  • Cell Physiology
  • Developmental Biology

Background:

  • The muscarinic cholinergic system plays a crucial role in regulating cardiac function.
  • L-type calcium current (ICa) is essential for cardiomyocyte excitation-contraction coupling.
  • Understanding developmental changes in ion channel modulation is vital for pediatric cardiology.

Purpose of the Study:

  • To investigate developmental alterations in the muscarinic cholinergic modulation of L-type Ca2+ current (ICa) in rabbit ventricular cells.
  • To elucidate the underlying molecular mechanisms, particularly the role of G proteins, in these developmental changes.

Main Methods:

  • Whole-cell patch-clamp electrophysiology was used to measure ICa in enzymatically isolated adult and newborn (1-4 days old) rabbit ventricular cells.

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  • Pharmacological agents including carbachol, isoproterenol, forskolin, and 5'-guanylyl imidodiphosphate [Gpp(NH)p] were employed to assess modulation.
  • Pertussis toxin pretreatment was used to investigate the involvement of inhibitory G proteins.

    • Main Results:

    • Carbachol significantly altered the sensitivity of adult ICa to isoproterenol and forskolin, while newborn ICa responses were diminished or abolished.
    • Gpp(NH)p mimicked and occluded some effects of carbachol, indicating G protein involvement, particularly an inhibitory pathway.
    • Pertussis toxin pretreatment abolished carbachol's inhibitory effects and enhanced forskolin's stimulatory effects, especially in newborn cells, suggesting a developmental decrease in Gi/o protein regulation.

    Conclusions:

    • The muscarinic cholinergic modulation of L-type ICa diminishes significantly after birth in rabbit ventricular cells.
    • This developmental shift is likely due to a reduced influence of inhibitory G proteins on adenylyl cyclase during the postnatal period.
    • These findings have implications for understanding age-related changes in cardiac electrophysiology and response to autonomic stimuli.