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Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels
07:17

Single-Cell Calcium Imaging for Studying the Activation of Calcium Ion Channels

Published on: December 13, 2024

Opioid modulation of calcium current in cultured sensory neurons: mu-modulation of baroreceptor input

M Hamra1, R S McNeil, M Runciman

  • 1Division of Pediatric Cardiology and Molecular Physiology and Biophysics, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas 77030, USA.

The American Journal of Physiology
|August 13, 1999
PubMed

Insights

Mu-opioid agonists inhibit calcium currents in nodose neurons, particularly in neonates. This G protein-mediated effect on aortic baroreceptor neurons may explain baroreflex attenuation.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cardiovascular Physiology

Background:

  • Mu-opioid receptors are involved in pain modulation and cardiovascular regulation.
  • Nodose sensory neurons play a critical role in baroreflex control.
  • Calcium currents (I(Ca)) are essential for neuronal excitability and neurotransmitter release.

Purpose of the Study:

  • To characterize mu-opioid modulation of I(Ca) in nodose sensory neurons, including aortic baroreceptor neurons.
  • To investigate the age-dependent effects of mu-opioids on I(Ca).
  • To elucidate the signaling pathways involved in mu-opioid action.

Main Methods:

  • Whole-cell patch-clamp recordings (open-patch and perforated-patch techniques).
  • Application of mu-opioid receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol enkephalin (DAGO).
  • Use of specific blockers (naloxone, pertussis toxin) and modulators (omega-conotoxin GVIA, guanosine nucleotides).

Main Results:

  • DAGO inhibited I(Ca) in a high percentage of neonatal nodose neurons (95%), with reduced sensitivity in juvenile (64%) and adult (61%) neurons.
  • DAGO's effect was naloxone-sensitive, G protein-mediated, and dependent on GTP, but not GDP.
  • In aortic baroreceptor neurons, DAGO's inhibition was concentration-dependent (IC(50) = 1.82 x 10(-8) M) and slowed I(Ca) activation.

Conclusions:

  • Mu-opioid modulation of I(Ca) in nodose neurons is age-dependent, with a more pronounced effect in neonates.
  • G protein signaling mediates the inhibitory effects of mu-opioids on I(Ca).
  • The findings provide a cellular mechanism for mu-opioid-induced attenuation of the baroreflex at the nucleus tractus solitarii level.

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