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Matsumoto S, Nishikawa T, Yoshida S, Ikeda M, Tanimoto T, Saiki C, Takeda M: Effects of potassium channel and Na+-Ca2+ exchange blockers on the responses of slowly adapting pulmonary stretch receptors to hyperinflation in flecainide-treated rats. Br J Pharmacol. 2001 Oct;134(3):682-90.
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. |
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