Effects of potassium channel and Na + ‐Ca 2+ exchange blockers on the responses of slowly adapting pulmonary stretch receptors to hyperinflation in flecainide‐treated rats

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 μg kg −1 veratridine‐induced SAR stimulation also inhibited hyperinflation‐induced stimulation of SARs. 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. 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. 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.British Journal of Pharmacology (2001) 134 , 682–690; doi: 10.1038/sj.bjp.0704277