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Specific bradycardic agents block the hyperpolarization-activated cation current in central neurons

H C Pape1

  • 1Abteilung für Neurophysiologie, Medizinische Fakultät, Ruhr-Universität, Bochum, Germany.

Neuroscience
|March 1, 1994
PubMed
Summary

Specific bradycardic agents, used to slow heart rate, can block the hyperpolarization-activated cation current (Ih) in central nervous system neurons. This may lead to unintended neuronal side effects, impacting brain activity.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Electrophysiology

Background:

  • Specific bradycardic agents target the hyperpolarization-activated cation current (Ih) in cardiac Purkinje fibers.
  • Ih channels are ubiquitous in mammalian excitable cells, including neurons.

Purpose of the Study:

  • To investigate the effects of specific bradycardic agents (UL-FS 49 and DK-AH 268) on central nervous system neurons.
  • To evaluate the influence of these agents on the hyperpolarization-activated cation current (Ih) in thalamocortical relay neurons.

Main Methods:

  • In vitro brain slice electrophysiology using guinea-pig thalamocortical relay neurons.
  • Local application of bradycardic agents at concentrations of 10(-5) to 10(-3) M.
  • Analysis of Ih current amplitude, activation curves, and I/V relationships.

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Main Results:

  • Bradycardic agents significantly reduced Ih current amplitude and altered its activation curve and I/V relationship.
  • Blockade was use-dependent and required Ih channel activation.
  • No significant effects were observed on currents independent of Ih or its gating properties.
  • Bradycardic agents blocked anomalous inward rectification and shifted membrane potential, promoting Ca(2+)-mediated burst activity.

Conclusions:

  • Specific bradycardic agents selectively and use-dependently block the conductance underlying Ih in neurons.
  • These agents do not alter Ih gating properties.
  • Potential neuronal side effects of bradycardia-producing agents warrant consideration due to Ih's presence in various neuronal populations.