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

Abstract

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.

Figure 1

Responses in P_T and SAR activity to veratridine before (a) and after (b) administration of flecainide (9 mg kg⁻¹). 100 s indicates the elapsed time between recordings. Responses in P_T and SAR activity to control inflation (inflation volume=1 V_T) and hyperinflation (inflation volume=3 V_T) before (c) and after (d) administration of flecainide (9 mg kg⁻¹) in the same rat.

Figure 2

Responses in SAR activity (a) and P_T (b) to veratridine at control inflation (inflation volume=1 V_T). Changes in SAR activity (c) and P_T (d) in response to control inflation and hyperinflation (inflation volume=3 V_T) before and after pretreatment with flecainide (9 mg kg⁻¹). Values are the means for 18 animals and the vertical bars show the s.e.means.

Figure 3

Responses in P_T and SAR activity to control inflation (inflation volume=1 V_T) and hyperinflation (inflation volume=3 V_T) before (a), during (b) and after administration of 4-AP (2 mg kg⁻¹) in a flecainide (9 mg kg⁻¹)-treated animal.

Figure 4

Changes in SAR activity (a) and P_T (b) in response to control inflation (inflation volume=1 V_T) and hyperinflation (inflation volume=3 V_T) before and after pretreatment with 4-AP. Values are the means for six flecainide (9 mg kg⁻¹)-treated animals and the vertical bars shown are the s.e.means.

Figure 5

Responses in P_T and SAR activity to control inflation (inflation volume=1 V_T) and hyperinflation (inflation volume=3 V_T) before (a) and after (b) administration of TEA (7 mg kg⁻¹) in a flecainide (9 mg kg⁻¹)-treated animal. Changes in SAR activity (c) and P_T (d) in response to control inflation and hyperinflation before and after pretreatment with TEA. Values are the means for six flecainide (9 mg kg⁻¹)-treated animals and the vertical bars show the s.e.means.

Figure 6

Responses in P_T and SAR activity to control inflation (inflation volume=1 V_T) and hyperinflation (inflation volume=3 V_T) before (a) and after (b) administration of KB-R7943 (3 mg kg⁻¹) in a flecainide (9 mg kg⁻¹)-treated animal. Changes in SAR activity (c) and P_T (d) in response to control inflation and hyperinflation before and after pretreatment with KB-R7943. Changes in SAR activity (e) induced by DMSO administration at control inflation. Values are the means for six flecainide (9 mg kg⁻¹)-treated animals and the vertical bars show the s.e.means.