Changes in pharyngeal respiratory muscle force produced by K+ channel blockade
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E van Lunteren1, H Vafaie, M Moyer
1Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Abstract:
The purpose of the present study was to determine whether the contractility of pharyngeal respiratory muscles can be augmented by altering membranous K+ channel conductance. The effects on twitch force of two K+ channel blockers, tetraethylammonium (TEA, 10 mM) and 4-aminopyridine (4-AP, 0.3 mM), were examined in vitro for sternohyoid and diaphragm muscle strips. Both agents augmented isometric twitch force of both muscles. In response to TEA twitch force of the sternohyoid muscle increased significantly more than that of the diaphragm (by 33 +/- 7 vs. 9 +/- 1%, P = 0.004), whereas with 4-AP the increase in twitch force of the sternohyoid muscle was comparable to that of the diaphragm (55 +/- 15 vs. 64 +/- 6%, P = 0.50). 4-AP shifted the force-frequency relationship of both muscles leftward but did not alter peak tetanic force, so that force with 4-AP exceeded that without drug at stimulation frequencies below 60 Hz. In contrast TEA reduced force at stimulation frequencies > 20 Hz. The isometric contraction times of both muscles was variably prolonged, more so with 4-AP (by 30 +/- 15% for the sternohyoid and 32 +/- 3% for the diaphragm) than with TEA (by 9 +/- 2% for the sternohyoid and 5 +/- 2% for the diaphragm). For the group of muscles and K+ channel blockers, the degree of augmentation of twitch force correlated with the degree of prolongation of contraction time (r = 0.82, P < 0.001), consistent with blocking delayed rectifier K+ channels as the mechanism of increasing muscle force.
Insights
Blocking specific potassium (K+) channels with drugs like tetraethylammonium (TEA) and 4-aminopyridine (4-AP) can increase the contractility of pharyngeal respiratory muscles, aiding muscle force generation.
Area of Science:
- Physiology
- Pharmacology
- Respiratory Muscle Research
Background:
- Pharyngeal respiratory muscles are crucial for breathing.
- Modulating ion channel activity is a potential strategy to enhance muscle function.
Purpose of the Study:
- To investigate if blocking membranous potassium (K+) channels can augment the contractility of pharyngeal respiratory muscles.
- To examine the effects of specific K+ channel blockers on muscle force and contraction dynamics.
Main Methods:
- In vitro study on sternohyoid and diaphragm muscle strips.
- Application of K+ channel blockers tetraethylammonium (TEA) and 4-aminopyridine (4-AP).
- Measurement of isometric twitch force, force-frequency relationships, and contraction times.
Main Results:
- Both TEA and 4-AP significantly augmented isometric twitch force in both sternohyoid and diaphragm muscles.
- 4-AP shifted the force-frequency relationship leftward, enhancing force at lower stimulation frequencies.
- TEA reduced force at higher stimulation frequencies, while both prolonged contraction times, with 4-AP having a more pronounced effect.
Conclusions:
- Blocking delayed rectifier K+ channels increases pharyngeal respiratory muscle force.
- The degree of force augmentation correlates with the prolongation of contraction time.
- Targeting K+ channels offers a potential therapeutic avenue for respiratory muscle weakness.