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

摘要

class="enumerated" style="list-style-type:decimal">The effects of K⁺ channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na⁺ – Ca²⁺ 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⁺-Ca²⁺ 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.