title: Excitatory mechanism of deflationary slowly adapting pulmonary stretch receptors in the rat lung.
abstract: The excitatory responses of deflationary slowly adapting pulmonary stretch receptor (SAR) activity to lung deflation ranging from approximately -15 to -25 cm of H(2)O for approximately 5 s were examined before and after administration of flecainide, a Na(+) channel blocker, and K(+) channel blockers, such as 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The experiments were performed in anesthetized, artificially ventilated rats after unilateral vagotomy. The deflationary SARs increased their activity during lung deflation and its effect became more pronounced by increasing the degree of negative pressure. During lung deflation the average values for the deflationary SAR adaptation index (AI) were below 40%. Intravenous administration of veratridine (50 microg/kg), an Na(+) channel opener, stimulated deflationary SAR activity: one maintained excitatory activity mainly during deflation and the other receptors showed a tonic discharge during both deflation and inflation. Despite the difference in deflationary SAR firing patterns after veratridine administration, flecainide treatment (6.0 mg/kg) blocked veratridine-induced deflationary SAR stimulation and also caused strong inhibition of the excitatory responses of deflationary SARs to lung deflation. Under these conditions, the average values for deflationary SAR AI were over 90%. The responses of deflationary SARs and deflationary SAR AI to lung deflation were not significantly altered by pretreatment with either 4-AP (0.7 and 2.0 mg/kg) or TEA (2.0 and 6.0 mg/kg). These results suggest that the excitatory effect of lung deflation on deflationary SAR activity is mediated by the activation of flecainide-sensitive Na(+) channels on the nerve terminals of deflationary SARs.
authors.affiliation: Department of Physiology, Nippon Dental University, School of Dentistry at Tokyo, Tokyo, Japan. matsu-s@tky.ndu.ac.jp
authors.forename: Shigeji
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Mizuho
authors.initials: M
authors.lastname: Ikeda
authors.forename: Toshimi
authors.initials: T
authors.lastname: Nishikawa
authors.forename: Shinki
authors.initials: S
authors.lastname: Yoshida
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanimoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Chikako
authors.initials: C
authors.lastname: Saiki
authors.forename: Mamoru
authors.initials: M
authors.lastname: Takeda
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology; D005424:Flecainide / Q000008:administration & dosage / Q000494:pharmacology; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D009186:Myelin Sheath / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011661:Pulmonary Stretch Receptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial; D012584:Sciatic Nerve / Q000502:physiology; D019789:Tetraethylammonium / Q000494:pharmacology; D014628:Vagotomy; D014701:Veratridine / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D000889:Anti-Arrhythmia Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium; D014701:Veratridine; D015761:4-Aminopyridine; D005424:Flecainide