The cardiac sympathetic co-transmitter galanin reduces acetylcholine release and vagal bradycardia

Implications for neural control of cardiac excitability

Neil Herring, James Cranley, Michael N. Lokale, Dan Li, Julia Shanks, Eric N. Alston, Beatrice M. Girard, Emma Carter, Rodney L. Parsons, Beth Habecker, David J. Paterson

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

The autonomic phenotype of congestive cardiac failure is characterised by high sympathetic drive and impaired vagal tone, which are independent predictors of mortality. We hypothesize that impaired bradycardia to peripheral vagal stimulation following high-level sympathetic drive is due to sympatho-vagal crosstalk by the adrenergic co-transmitters galanin and neuropeptide-Y (NPY). Moreover we hypothesize that galanin acts similarly to NPY by reducing vagal acetylcholine release via a receptor mediated, protein kinase-dependent pathway. Prolonged right stellate ganglion stimulation (10Hz, 2min, in the presence of 10μM metoprolol) in an isolated guinea pig atrial preparation with dual autonomic innervation leads to a significant (p2 receptor antagonist BIIE 0246 at all time points (1μM, n=6). Exogenous galanin (n=6, 50-500nM) also reduced the heart rate response to vagal stimulation but had no effect on the response to carbamylcholine that produced similar degrees of bradycardia (n=6). Galanin (500nM) also significantly attenuated the release of 3H-acetylcholine from isolated atria during field stimulation (5Hz, n=5). The effect of galanin on vagal bradycardia could be abolished by the galanin receptor antagonist M40 (n=5). Importantly the GalR 1 receptor was immunofluorescently co-localised with choline acetyl-transferase containing neurons at the sinoatrial node. The protein kinase C inhibitor calphostin (100nM, n=6) abolished the effect of galanin on vagal bradycardia whilst the protein kinase A inhibitor H89 (500nM, n=6) had no effect. These results demonstrate that prolonged sympathetic activation releases the slowly diffusing adrenergic co-transmitter galanin in addition to NPY, and that this contributes to the attenuation in vagal bradycardia via a reduction in acetylcholine release. This effect is mediated by GalR 1 receptors on vagal neurons coupled to protein kinase C dependent signalling pathways. The role of galanin may become more important following an acute injury response where galanin expression is increased.

Original languageEnglish (US)
Pages (from-to)667-676
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume52
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

Galanin
Bradycardia
Acetylcholine
Neuropeptide Y
Protein Kinase Inhibitors
Adrenergic Agents
Protein Kinase C
Galanin Receptors
Stellate Ganglion
Neurons
Sinoatrial Node
Metoprolol
Protein C Inhibitor
Carbachol
Transferases
Cyclic AMP-Dependent Protein Kinases
Choline
Protein Kinases
Guinea Pigs
Heart Failure

Keywords

  • Acetylcholine
  • Autonomic nervous system
  • Co-transmitters
  • Heart rate
  • Sympathetic
  • Vagus

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

The cardiac sympathetic co-transmitter galanin reduces acetylcholine release and vagal bradycardia : Implications for neural control of cardiac excitability. / Herring, Neil; Cranley, James; Lokale, Michael N.; Li, Dan; Shanks, Julia; Alston, Eric N.; Girard, Beatrice M.; Carter, Emma; Parsons, Rodney L.; Habecker, Beth; Paterson, David J.

In: Journal of Molecular and Cellular Cardiology, Vol. 52, No. 3, 03.2012, p. 667-676.

Research output: Contribution to journalArticle

Herring, Neil ; Cranley, James ; Lokale, Michael N. ; Li, Dan ; Shanks, Julia ; Alston, Eric N. ; Girard, Beatrice M. ; Carter, Emma ; Parsons, Rodney L. ; Habecker, Beth ; Paterson, David J. / The cardiac sympathetic co-transmitter galanin reduces acetylcholine release and vagal bradycardia : Implications for neural control of cardiac excitability. In: Journal of Molecular and Cellular Cardiology. 2012 ; Vol. 52, No. 3. pp. 667-676.
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