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

<jats:p> <jats:list list-type="explicit-label"> <jats:list-item><jats:p>The effects of K<jats:sup>+</jats:sup> channel blockers, such as 4‐aminopyridine (4‐AP) and tetraethylammonium (TEA), and a reverse‐mode Na<jats:sup>+</jats:sup> – Ca<jats:sup>2+</jats:sup> 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<jats:sup>+</jats:sup> channel blocker flecainide. The administration of flecainide (9 mg kg<jats:sup>−1</jats:sup>) at a dose greater than that which abolished 50 μg kg<jats:sup>−1</jats:sup> veratridine‐induced SAR stimulation also inhibited hyperinflation‐induced stimulation of SARs.</jats:p></jats:list-item> <jats:list-item><jats:p>In flecainide‐treated animals, administration of 4‐AP (0.7 and 2 mg kg<jats:sup>−1</jats:sup>) stimulated SAR activity during normal inflation and also caused a partial blockade of hyperinflation‐induced SAR inhibition.</jats:p></jats:list-item> <jats:list-item><jats:p>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<jats:sup>−1</jats:sup>) or KB‐R7943 (1 and 3 mg kg<jats:sup>−1</jats:sup>), but both K<jats:sup>+</jats:sup> channel and Na<jats:sup>+</jats:sup>‐Ca<jats:sup>2+</jats:sup> exchange blockers partially attenuated hyperinflation‐induced SAR inhibition.</jats:p></jats:list-item> <jats:list-item><jats:p>These results suggest that hyperinflation‐induced SAR inhibition in the presence of flecainide (9 mg kg<jats:sup>−1</jats:sup>) involves the activation of several K<jats:sup>+</jats:sup> conductance pathways.</jats:p></jats:list-item> </jats:list> </jats:p><jats:p><jats:italic>British Journal of Pharmacology</jats:italic> (2001) <jats:bold>134</jats:bold>, 682–690; doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0704277">10.1038/sj.bjp.0704277</jats:ext-link></jats:p>