CHANGES IN PHARYNGEAL RESPIRATORY MUSCLE FORCE PRODUCED BY K+ CHANNELBLOCKADE

The purpose of the present study was to determine whether the contract ility of pharyngeal respiratory muscles can be augmented by altering m embranous K+ channel conductance. The effects on twitch force of two K + channel blockers, tetraethylammonium (TEA, 10 mM) and 4-aminopyridin e (4-AP, 0.3 mM), were examined in vitro for sternohyoid and diaphragm muscle strips. Both agents augmented isometric twitch force of both m uscles. In response to TEA twitch force of the sternohyoid muscle incr eased 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 o f the sternohyoid muscle was comparable to that of the diaphragm (55 /- 15 vs. 64 +/- 6%, P = 0.50). 4-AP shifted the force-frequency relat ionship of both muscles leftward but did not alter peak tetanic force, so that force with 4-AP exceeded that without drug at stimulation fre quencies below 60 Hz. In contrast TEA reduced force at stimulation fre quencies > 20 Hz. The isometric contraction times of both muscles was variably prolonged, more so with 4-AP (by 30 +/- 15% for the sternohyo id 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 c orrelated with the degree of prolongation of contraction time (r = 0.8 2, P < 0.001), consistent with blocking delayed rectifier K+ channels as the mechanism of increasing muscle force.