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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
Author(s) -
Matsumoto Shigeji,
Nishikawa Toshimi,
Yoshida Shinki,
Ikeda Mizuho,
Tanimoto Takeshi,
Saiki Chikako,
Takeda Mamoru
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704277
Subject(s) - flecainide , potassium channel blocker , channel blocker , chemistry , tetraethylammonium , stimulation , potassium channel , veratridine , medicine , pharmacology , endocrinology , potassium , sodium channel , sodium , calcium , organic chemistry , atrial fibrillation
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