Premium
Mechanisms of galanin inhibition of cardiac parasympathetic transmission
Author(s) -
Habecker Beth A,
Nokale Michael N.E.,
Li Dan,
Paterson David J.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1201-d
Subject(s) - galanin , medicine , vagus nerve , endocrinology , carbachol , acetylcholine , parasympathetic nervous system , neuropeptide , galanin receptor , bradycardia , neurotransmission , vagus nerve stimulation , stimulation , autonomic nervous system , chemistry , heart rate , receptor , blood pressure
Dual innervation by sympathetic ‐ parasympathetic inputs provides the final common pathway for all autonomic cardiac control. Cardiac parasympathetic transmission is inhibited by release of the neuropeptide galanin from cardiac sympathetic neurons. Galanin inhibition of vagal transmission is generally well‐documented, but surprisingly little is known about the details of its mechanism of action. The objective of this study was to identify the mechanisms that underlie galanin inhibition of cardiac parasympathetic transmission. We investigated galanin regulation of vagal transmission in guinea pig isolated atria with or without an intact vagus nerve. In pilot experiments galanin (250 nM) had little effect on carbachol‐induced bradycardia (30, 60, 90 nM carbachol), suggesting that galanin inhibits vagal transmission through a pre‐synaptic mechanism. Field stimulation (10 Hz, 15 V) of isolated atria revealed that 500 nM galanin inhibited [3H]‐acetylcholine release from cardiac parasympathetic nerves by ~35%. Vagal nerve stimulation(5 Hz) triggers bradycardia in vitro. Blockade of protein kinase A activity with H‐89 (0.5 μM) did not prevent galanin (250 nM) inhibition of vagally‐induced bradycardia. These data suggest that galanin inhibits cardiac parasympathetic transmission by pre‐synaptic inhibition of acetylcholine release through a protein kinase A‐independent mechanism. This work was supported by NIH R01 HL68231 and the British Heart Foundation.