Functional expression of "cardiac-type" Nav1.5 sodium channel in canine intracardiac ganglia.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Scornik
Fabiana S
FS
Masonic Medical Research Laboratory, Utica, New York 13501, USA. fscornik@mmrl.edu
Desai
Mayurika
M
Brugada
Ramón
R
Guerchicoff
Alejandra
A
Pollevick
Guido D
GD
Antzelevitch
Charles
C
Pérez
Guillermo J
GJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004285:Dogs; D005725:Ganglia, Autonomic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006321:Heart / Q000187:drug effects / Q000294:innervation*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015222:Sodium Channels / Q000096:biosynthesis / Q000235:genetics*; D013779:Tetrodotoxin / Q000494:pharmacology
D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D015222:Sodium Channels; D013779:Tetrodotoxin; D012313:RNA