Affordable Access

deepdyve-link
Publisher Website

Multiple nickel-sensitive targets elicit cardiac arrhythmia in isolated mouse hearts after pituitary adenylate cyclase-activating polypeptide-mediated chronotropy.

Authors
  • Tevoufouet, Etienne E1
  • Nembo, Erastus N2
  • Distler, Fabian2
  • Neumaier, Felix2
  • Hescheler, Jürgen2
  • Nguemo, Filomain2
  • Schneider, Toni3
  • 1 Institute of Neurophysiology, University of Köln, Robert-Koch-Str. 39, D-50931 Köln, Germany. Electronic address: [email protected]
  • 2 Institute of Neurophysiology, University of Köln, Robert-Koch-Str. 39, D-50931 Köln, Germany.
  • 3 Institute of Neurophysiology, University of Köln, Robert-Koch-Str. 39, D-50931 Köln, Germany. Electronic address: [email protected]
Type
Published Article
Journal
Pharmacological Research
Publisher
Elsevier
Publication Date
Dec 19, 2016
Volume
117
Pages
140–147
Identifiers
DOI: 10.1016/j.phrs.2016.12.025
PMID: 28007571
Source
Medline
Keywords
License
Unknown

Abstract

The pituitary adenylate cyclase-activating polypeptide (PACAP)-27 modulates various biological processes, from the cellular level to function specification. However, the cardiac actions of this neuropeptide are still under intense studies. Using control (+|+) and mice lacking (-|-) either R-type (Cav2.3) or T-type (Cav3.2) Ca2+ channels, we investigated the effects of PACAP-27 on cardiac activity of spontaneously beating isolated perfused hearts. Superfusion of PACAP-27 (20nM) caused a significant increase of baseline heart frequency in Cav2.3(+|+) (156.9±10.8 to 239.4±23.4 bpm; p<0.01) and Cav2.3(-|-) (190.3±26.4 to 270.5±25.8 bpm; p<0.05) hearts. For Cav3.2, the heart rate was significantly increased in Cav3.2(-|-) (133.1±8.5 bpm to 204.6±27.9 bpm; p<0.05) compared to Cav3.2(+|+) hearts (185.7±11.2 bpm to 209.3±22.7 bpm). While the P wave duration and QTc interval were significantly increased in Cav2.3(+|+) and Cav2.3(-|-) hearts following PACAP-27 superfusion, there was no effect in Cav3.2(+|+) and Cav3.2(-|-) hearts. The positive chronotropic effects observed in the four study groups, as well as the effect on P wave duration and QTc interval were abolished in the presence of Ni2+ (50μM) and PACAP-27 (20nM) in hearts from Cav2.3(+|+) and Cav2.3(-|-) mice. In addition to suppressing PACAP's response, Ni2+ also induced conduction disturbances in investigated hearts. In conclusion, the most Ni2+-sensitive Ca2+ channels (R- and T-type) may modulate the PACAP signaling cascade during cardiac excitation in isolated mouse hearts, albeit to a lesser extent than other Ni2+-sensitive targets.

Report this publication

Statistics

Seen <100 times