Flecainide inhibits the stimulatory effect of veratridine on the response of airway mechanoreceptors to maintained inflations in rats.
ABSTRACT the purpose of the present study was to investigate (a) whether maintained inflations result in the inhibition of slowly adapting pulmonary stretch receptor (SAR) discharge to elicit an abrupt change in receptor activity and (b) whether pretreatment with veratridine, a Na(+) channel opener, and/or flecainide, a Na(+) channel blocker, alters the responses of SAR properties to maintained inflations.
we measured the properties of SAR activity during maintained inflations at different pressures in 31 anesthetized, artificially ventilated rats with unilateral vagotomy.
During maintained inflations (approximately 5, 10 and 15 cmH(2)O) for about 5s, the procedures did not produce the induction of inhibition of either 16 low-threshold SARs (firing during both inflation and deflation) or 15 high-threshold SARs (firing during inflation only). In these preparations, the excitatory responses of SARs to maintained inflations at three different pressures were markedly enhanced after administration of veratridine (50 μg/kg), but under such conditions, the inhibition of SAR discharges was not observed. In the same SAR preparations, after flecainide treatment (9 mg/kg) sufficient for the blockade of veratridine (50 μg/kg)-induced SAR stimulation, maintained inflations at higher pressures (10 and 15 cmH(2)O) greatly inhibited SAR discharges. Under these conditions, the inhibition of SAR discharges was not observed during maintained inflations at 5 cmH(2)O.
These results suggest that neither low-threshold SARs nor high-threshold SARs in the rat lung are deactivated during maintained inflations at higher pressures.
- SourceAvailable from: Mamoru Takeda[Show abstract] [Hide abstract]
ABSTRACT: The effects of K+ channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA), and a reverse-mode Na+ – Ca2+ 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+-Ca2+ 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 11/2001; · 4.99 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: 1. Intracellular microelectrodes recorded the receptor potential and receptor current in the neurons of spider slit sense organs during mechanical stimulation of the slits. 2. Mechanical stimulation produced two patterns of action potential discharge, corresponding to the two groups of neurons described previously by electrical stimulation. 3. Tetrodotoxin eliminated the action potentials and revealed a receptor potential with both static and adapting components. Voltage clamp gave an inward receptor current with a similar time course. 4. Replacement of sodium ions in the bath reversibly eliminated the receptor current, indicating that it is carried by sodium ions. However, this effect was comparatively slow, suggesting that the tips of the sensory dendrites lie in a chemically restricted environment.Journal of Neurophysiology 01/1995; 72(6):3026-8. · 3.04 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To elucidate the characteristics of vagal afferent fibers arising from rat lungs, single-unit activity from pulmonary stretch receptors and two other types of pulmonary receptors was recorded. In the latter, one type of receptor, termed deflation-sensitive receptors in this study, was stimulated only in the expiratory phase of normal respiration. Moreover, this type of receptor exhibited persistent discharges resulting in a train or burst of impulses with collapse and forced deflation, respectively. The decrease of discharge frequency during collapse was slow and the average adaptation index was 20%, indicating a slowly adapting characteristic. Upon forced deflation, the discharge frequency increased with increasing negative pressure to -158 mm H2O intratracheal pressure. The other type of receptor, termed irritant-like receptors, responded to both deflation and inflation. In addition, they displayed rapidly adapting and irregular discharges during maintained inflation. These results indicate that rat vagus nerves deliver afferent information from at least three types of pulmonary receptors: pulmonary stretch and lung irritant-like receptors and the receptors specifically sensitive to expiration or lung deflation. Furthermore, the possibility is postulated that vagal deflation-sensitive receptors are related to the peripheral mechanism in normal respiration and Hering-Breuer deflation reflex in rats.Experimental Neurology 07/1986; 92(3):541-52. · 4.62 Impact Factor