Effects of potassium channel and Na+-Ca2+ exchange blockers on the responses of slowly adapting pulmonary stretch receptors to hyperinflation in flecainide-treated rats.

1. The effects of K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na(+)-Ca(2+) exchange blocker, 2-[2-[4-(4-nitrobenzyloxyl) phenyl] ethyl] isothiourea methanesulphonate (KB-R7943), on the responses of slowly adapting pulmonary stretch receptor activity to hyperinflation (inflation volume=3 tidal volumes) were investigated in anaesthetized, artificially ventilated, unilaterally vagotomized rats after pretreatment with a Na(+) channel blocker flecainide. The administration of flecainide (9 mg kg(-1)) at a dose greater than that which abolished 50 microg kg(-1) veratridine-induced SAR stimulation also inhibited hyperinflation-induced stimulation of SARs. 2. In flecainide-treated animals, administration of 4-AP (0.7 and 2 mg kg(-1)) stimulated SAR activity during normal inflation and also caused a partial blockade of hyperinflation-induced SAR inhibition. 3. The discharges of SARs during normal inflation in flecainide-treated animals were not significantly altered by administration of either TEA (2 and 7 mg kg(-1)) or KB-R7943 (1 and 3 mg kg(-1)), but both K(+) channel and Na(+)-Ca(2+) exchange blockers partially attenuated hyperinflation-induced SAR inhibition. 4. These results suggest that hyperinflation-induced SAR inhibition in the presence of flecainide (9 mg kg(-1)) involves the activation of several K(+) conductance pathways.