Changes in pharyngeal respiratory muscle force produced by K+ channel blockade

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.