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Spontaneous transient outward currents and delayed rectifier K+ current: effects of hypoxia
C Vandier1, M Delpech, P Bonnet
1Unité Mixte de Recherche (UMR) Centre National de la Recherche Scientifique 6542, Physiologie des Cellules Cardiaques et Vasculaires, Faculté des Sciences, 37200 Tours Cedex, France.
The American Journal of Physiology
|August 5, 1998
Summary
This study reveals that hypoxia and thapsigargin reduce spontaneous transient outward currents (STOCs) in rabbit pulmonary artery smooth muscle cells. These effects are mediated by calcium, impacting potassium channel function.
Area of Science:
- Cardiovascular Physiology
- Cellular Electrophysiology
- Smooth Muscle Biology
Background:
- Pulmonary artery smooth muscle cells regulate vascular tone.
- Potassium channels play a critical role in smooth muscle cell membrane potential and function.
- Spontaneous transient outward currents (STOCs) are mediated by calcium-activated potassium channels.
Purpose of the Study:
- To investigate the electrophysiological properties of rabbit intrapulmonary artery smooth muscle cells.
- To characterize the nature of spontaneous transient outward currents (STOCs) and steady-state outward currents.
- To determine the effects of hypoxia and sarcoplasmic/endoplasmic reticulum calcium stores on these currents.
Main Methods:
- Voltage clamp using the perforated-patch configuration of the patch-clamp technique.
- Application of pharmacological agents including tetraethylammonium, 4-aminopyridine, ryanodine, caffeine, and thapsigargin.
- Exposure to hypoxic conditions (PO2 = 10 mmHg).
Main Results:
- STOCs were identified as Ca2+-activated K+ currents, and steady-state outward current as delayed rectifier K+ current.
- STOCs exhibited quantized amplitudes and a mean frequency of 5.51 Hz.
- Ryanodine, caffeine, thapsigargin, and hypoxia significantly decreased STOCs.
- Hypoxia's effect on STOCs was partially reversible with thapsigargin.
- Hypoxia and thapsigargin reduced steady-state outward current via a Ca2+-dependent mechanism.
Conclusions:
- Hypoxia and impaired Ca2+ handling (thapsigargin) inhibit Ca2+-activated K+ channels in pulmonary artery smooth muscle.
- The steady-state outward current is also diminished by hypoxia through a Ca2+-dependent pathway.
- These findings suggest complex interactions between oxygen levels, intracellular calcium, and ion channel activity in regulating vascular smooth muscle.