Effects of potassium channel and Na+-Ca2+ exchange blockers on the responses of slowly adapting pulmonary stretch receptors to hyperinflation in flecainide-treated rats.
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.
Matsumoto
S
S
Department of Physiology, Nippon Dental University, School of Dentistry at Tokyo, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan.
Nishikawa
T
T
Yoshida
S
S
Ikeda
M
M
Tanimoto
T
T
Saiki
C
C
Takeda
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005424:Flecainide / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011661:Pulmonary Stretch Receptors / Q000187:drug effects* / Q000502:physiology; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000502:physiology; D013990:Tidal Volume / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D019831:Sodium-Calcium Exchanger; D005424:Flecainide