BACKGROUND: The autonomic nervous system has been implicated in several arrhythmogenic diseases, including long QT syndrome type 3 (LQT3) and Brugada syndrome. Scarce information on the cellular components of the intrinsic cardiac ganglia from higher mammals has limited our understanding of the role of the autonomic nervous system in such diseases. OBJECTIVES: The purpose of this study was to isolate and characterize the electrophysiologic properties of canine intracardiac neurons. METHODS: Action potentials (APs) and ionic currents were studied in enzymatically dissociated canine intracardiac neurons under current and voltage clamp conditions. Immunohistochemical and reverse transcription-polymerase chain reaction analysis was performed using freshly isolated intracardiac ganglia. RESULTS: APs recorded from intracardiac neurons displayed a tetrodotoxin-resistant (TTX-R) component. TTX-R APs were abolished in the absence of sodium but persisted in the absence of external calcium. Immunohistochemical studies showed the presence of TTX-R sodium channels in these ganglia. Sodium currents were characterized by two components with different affinities for TTX: a tetrodotoxin-sensitive (TTX-S) component and a TTX-R component. TTX-S current inactivation was characteristic of neuronal sodium currents, whereas TTX-R current inactivation time constants were similar to those previously reported for Na(v)1.5 channels. TTX sensitivity (IC(50) = 1.17 microM) of the TTX-R component was in the range reported for Na(v)1.5 channels. Expression of Na(v)1.5 channels in intracardiac ganglia was confirmed by PCR analysis and sequencing. CONCLUSION: Our results suggest that canine intracardiac neurons functionally express Na(v)1.5 channels. These findings open an exciting new door to our understanding of autonomically modulated arrhythmogenic diseases linked to mutations in Na(v)1.5 channels, including Brugada syndrome and LQT3.
BACKGROUND: The autonomic nervous system has been implicated in several arrhythmogenic diseases, including long QT syndrome type 3 (LQT3) and Brugada syndrome. Scarce information on the cellular components of the intrinsic cardiac ganglia from higher mammals has limited our understanding of the role of the autonomic nervous system in such diseases. OBJECTIVES: The purpose of this study was to isolate and characterize the electrophysiologic properties of canine intracardiac neurons. METHODS: Action potentials (APs) and ionic currents were studied in enzymatically dissociated canine intracardiac neurons under current and voltage clamp conditions. Immunohistochemical and reverse transcription-polymerase chain reaction analysis was performed using freshly isolated intracardiac ganglia. RESULTS: APs recorded from intracardiac neurons displayed a tetrodotoxin-resistant (TTX-R) component. TTX-R APs were abolished in the absence of sodium but persisted in the absence of external calcium. Immunohistochemical studies showed the presence of TTX-Rsodium channels in these ganglia. Sodium currents were characterized by two components with different affinities for TTX: a tetrodotoxin-sensitive (TTX-S) component and a TTX-R component. TTX-S current inactivation was characteristic of neuronal sodium currents, whereas TTX-R current inactivation time constants were similar to those previously reported for Na(v)1.5 channels. TTX sensitivity (IC(50) = 1.17 microM) of the TTX-R component was in the range reported for Na(v)1.5 channels. Expression of Na(v)1.5 channels in intracardiac ganglia was confirmed by PCR analysis and sequencing. CONCLUSION: Our results suggest that canine intracardiac neurons functionally express Na(v)1.5 channels. These findings open an exciting new door to our understanding of autonomically modulated arrhythmogenic diseases linked to mutations in Na(v)1.5 channels, including Brugada syndrome and LQT3.
Authors: R Dumaine; J A Towbin; P Brugada; M Vatta; D V Nesterenko; V V Nesterenko; J Brugada; R Brugada; C Antzelevitch Journal: Circ Res Date: 1999-10-29 Impact factor: 17.367
Authors: Sebastian K G Maier; Ruth E Westenbroek; Kenneth A Schenkman; Eric O Feigl; Todd Scheuer; William A Catterall Journal: Proc Natl Acad Sci U S A Date: 2002-03-12 Impact factor: 11.205
Authors: Peter R Strege; Yijun Ou; Lei Sha; Adam Rich; Simon J Gibbons; Joseph H Szurszewski; Michael G Sarr; Gianrico Farrugia Journal: Am J Physiol Gastrointest Liver Physiol Date: 2003-07-31 Impact factor: 4.052
Authors: Y Ou; S J Gibbons; S M Miller; P R Strege; A Rich; M A Distad; M J Ackerman; J L Rae; J H Szurszewski; G Farrugia Journal: Neurogastroenterol Motil Date: 2002-10 Impact factor: 3.598
Authors: Augustus O Grant; Michael P Carboni; Valentina Neplioueva; C Frank Starmer; Mirella Memmi; Carlo Napolitano; Silvia Priori Journal: J Clin Invest Date: 2002-10 Impact factor: 14.808
Authors: Xiao-Ping Liu; Julian R A Wooltorton; Sophie Gaboyard-Niay; Fu-Chia Yang; Anna Lysakowski; Ruth Anne Eatock Journal: J Neurophysiol Date: 2016-03-02 Impact factor: 2.714