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Article ; Online: Action potential conduction in the mouse and rat vagus nerve is dependent on multiple voltage-gated sodium channels (Na

Nair, Sanjay S / Pavelkova, Nikoleta / Murphy, Claire M / Kollarik, Marian / Taylor-Clark, Thomas E

2023 Volume 130, Issue 3, Page(s) 684–693

Abstract: Action potential (AP) conduction depends on voltage-gated sodium channels, of which there are nine subtypes. The vagus nerve, comprising sensory afferent fibers and efferent parasympathetic fibers, provides autonomic regulation of visceral organs, but ... ...

Abstract	Action potential (AP) conduction depends on voltage-gated sodium channels, of which there are nine subtypes. The vagus nerve, comprising sensory afferent fibers and efferent parasympathetic fibers, provides autonomic regulation of visceral organs, but the voltage-gated sodium channels (Na
MeSH term(s)	Mice ; Rats ; Animals ; Action Potentials/physiology ; Voltage-Gated Sodium Channels/physiology ; Tetrodotoxin/pharmacology ; Vagus Nerve/physiology
Chemical Substances	PF-05089771 ; A 803467 ; Voltage-Gated Sodium Channels ; Tetrodotoxin (4368-28-9)
Language	English
Publishing date	2023-08-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00041.2023
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Article ; Online: Vague no more: Evidence of divergent central pathways of sensory nerves innervating the human airways.

Taylor-Clark, Thomas E / Kollarik, Marian

The Journal of physiology

2020 Volume 598, Issue 24, Page(s) 5597–5598

MeSH term(s)	Afferent Pathways ; Brain ; Humans ; Nodose Ganglion ; Respiratory System
Language	English
Publishing date	2020-10-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP280742
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Article ; Online: Role of Na

Kollarik, Marian / Ru, Fei / Pavelkova, Nikoleta / Mulcahy, John / Hunter, John / Undem, Bradley J

British journal of pharmacology

2021 Volume 179, Issue 2, Page(s) 242–251

Abstract: Background and purpose: The purpose of this study was to determine the role of Na: Experimental approach: Bronchial branches of the vagus nerve were dissected from human donor tissue. The C-wave of the electrically evoked compound action potential ... ...

Abstract	Background and purpose: The purpose of this study was to determine the role of Na Experimental approach: Bronchial branches of the vagus nerve were dissected from human donor tissue. The C-wave of the electrically evoked compound action potential was quantified in the absence and presence of increasing concentrations of the selective Na Key results: The selective Na Conclusions and implications: Na
MeSH term(s)	Action Potentials ; Bronchi ; Heart Rate ; Humans ; Tetrodotoxin ; Vagus Nerve/physiology
Chemical Substances	Tetrodotoxin (4368-28-9)
Language	English
Publishing date	2021-11-08
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.15686
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Article ; Online: Contribution of tetrodotoxin-sensitive, voltage-gated sodium channels (Na

Hadley, Stephen / Patil, Mayur J / Pavelkova, Nikoleta / Kollarik, Marian / Taylor-Clark, Thomas E

American journal of physiology. Regulatory, integrative and comparative physiology

2021 Volume 321, Issue 5, Page(s) R672–R686

Abstract: Action potentials depend on voltage-gated sodium channels ( ... ...

Abstract	Action potentials depend on voltage-gated sodium channels (Na
MeSH term(s)	Action Potentials/drug effects ; Animals ; Esophagus/innervation ; Gastrointestinal Motility ; Mechanoreceptors/drug effects ; Mechanoreceptors/metabolism ; Mechanotransduction, Cellular/drug effects ; Mice, Inbred C57BL ; Mice, Transgenic ; Sodium Channel Blockers/pharmacology ; Stress, Mechanical ; Tetrodotoxin/pharmacology ; Time Factors ; Vagus Nerve/drug effects ; Vagus Nerve/metabolism ; Voltage-Gated Sodium Channels/drug effects ; Voltage-Gated Sodium Channels/genetics ; Voltage-Gated Sodium Channels/metabolism ; Mice
Chemical Substances	Sodium Channel Blockers ; Voltage-Gated Sodium Channels ; Tetrodotoxin (4368-28-9)
Language	English
Publishing date	2021-09-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	603839-6
ISSN	1522-1490 ; 0363-6119
ISSN (online)	1522-1490
ISSN	0363-6119
DOI	10.1152/ajpregu.00199.2021
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Article ; Online: Phenotypic distinctions between the nodose and jugular TRPV1-positive vagal sensory neurons in the cynomolgus monkey.

Kollarik, Marian / Ru, Fei / Undem, Bradley J

Neuroreport

2019 Volume 30, Issue 8, Page(s) 533–537

Abstract: Vagal capsaicin-sensitive afferent C-fibers play an important role in the maintenance of visceral homeostasis and contribute to symptoms in visceral diseases. Based on their developmental origin two functionally distinct types of vagal C-fibers are ... ...

Abstract	Vagal capsaicin-sensitive afferent C-fibers play an important role in the maintenance of visceral homeostasis and contribute to symptoms in visceral diseases. Based on their developmental origin two functionally distinct types of vagal C-fibers are recognized: those with neurons in the vagal nodose ganglia (derived from epibranchial placodes) and in the vagal jugular ganglia (from neural crest). Studies in nonprimate species demonstrated that the vagal nodose and jugular C-fibers differ in activation profile, neurotrophic regulation, and expression of neurotransmitters. We hypothesized that the expression of selected markers related to key phenotypic properties of vagal C-fibers in the cynomolgus monkey is similar to that reported in nonprimate species. We performed single-cell RT-PCR on nodose and jugular putative C-fiber (TRPV1-positive) neurons isolated from the cynomolgus monkey. We found that the expression of purinergic P2X receptors that underlie selective responsiveness of nodose C-fiber terminals to ATP was conserved in that P2X2 and P2X3 subunits were expressed in nodose, but only P2X3 subunit was expressed in jugular TRPV1-positive neurons. Also conserved was the preferential expression of neurotrophic receptor TrkB in the nodose and preprotachykinin-A in the jugular TRPV1-positive neurons. Several key distinctions in gene expression between nodose and jugular TRPV1-positive (C-fiber) neurons that have been noted in mice, rats, and guinea pigs, are conserved in the cynomolgus monkey. Our results support the translatability of distinct vagal C-fiber phenotypes to primates.
MeSH term(s)	Animals ; Macaca fascicularis ; Nerve Fibers, Unmyelinated/metabolism ; Nodose Ganglion/metabolism ; Phenotype ; Protein Precursors/metabolism ; Receptors, Purinergic P2X2/metabolism ; Receptors, Purinergic P2X3/metabolism ; Sensory Receptor Cells/metabolism ; Species Specificity ; TRPV Cation Channels/metabolism ; Tachykinins/metabolism
Chemical Substances	Protein Precursors ; Receptors, Purinergic P2X2 ; Receptors, Purinergic P2X3 ; TRPV Cation Channels ; Tachykinins ; preprotachykinin
Language	English
Publishing date	2019-03-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1049746-8
ISSN	1473-558X ; 0959-4965
ISSN (online)	1473-558X
ISSN	0959-4965
DOI	10.1097/WNR.0000000000001231
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Article ; Online: Comprehensive analysis of acidic pharyngeal reflux before and after proton pump inhibitor treatment in patients with suspected laryngopharyngeal reflux.

Duricek, Martin / Banovcin, Peter / Halickova, Tatiana / Hyrdel, Rudolf / Kollarik, Marian

European journal of gastroenterology & hepatology

2020 Volume 32, Issue 2, Page(s) 166–174

Abstract: Objectives: The usefulness of pharyngeal pH monitoring in patients with symptoms attributed to laryngopharyngeal reflux (LPR) has been questioned. One problem is the uncertainty whether the pharyngeal pH monitoring captures the aspects of LPR which are ... ...

Abstract	Objectives: The usefulness of pharyngeal pH monitoring in patients with symptoms attributed to laryngopharyngeal reflux (LPR) has been questioned. One problem is the uncertainty whether the pharyngeal pH monitoring captures the aspects of LPR which are responsible for symptoms. We aimed to gain more insight into this problem by performing a comprehensive analysis of acidic pharyngeal reflux before and after the treatment with proton pump inhibitors (PPIs) in patients with suspected LPR. Methods: We used simultaneous pharyngeal and distal esophageal 24-hour pH/impedance monitoring to establish the gastroesophageal origin of pharyngeal reflux, and an unbiased approach to analysis by evaluating a whole range of pharyngeal reflux acidity (pH < 6, pH < 5.5, pH < 5.0, pH < 4.5 and pH < 4.0). Results: PPI treatment substantially (by ~50%) improved the symptoms attributed to LPR. In contrast, PPI did not reduce the number of pharyngeal reflux episodes or duration of pharyngeal acid exposure at any pH level. This was also true in a subgroup of patients considered to be good responders to PPI (symptoms improvement by ~75%). Furthermore, good responders did not have more acidic pharyngeal reflux than the patients who were less responsive to PPI. Conclusions: PPI treatment did not reduce acidic pharyngeal reflux despite substantially improving the symptoms attributed to LPR. This may be because pharyngeal pH monitoring does not quantitatively capture the aspects of LPR responsible for symptoms or because acid causes the symptoms also by mechanisms other than LPR. Our results argue against the utility of pharyngeal pH monitoring in patients with suspected LPR.
MeSH term(s)	Esophageal pH Monitoring ; Heartburn ; Humans ; Hydrogen-Ion Concentration ; Laryngopharyngeal Reflux/diagnosis ; Laryngopharyngeal Reflux/drug therapy ; Pharynx ; Proton Pump Inhibitors/therapeutic use
Chemical Substances	Proton Pump Inhibitors
Language	English
Publishing date	2020-01-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1034239-4
ISSN	1473-5687 ; 0954-691X
ISSN (online)	1473-5687
ISSN	0954-691X
DOI	10.1097/MEG.0000000000001584
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Article ; Online: Novel computer algorithm for cough monitoring based on octonions.

Klco, Peter / Kollarik, Marian / Tatar, Milos

Respiratory physiology & neurobiology

2018 Volume 257, Page(s) 36–41

Abstract: The objective assessment of cough frequency is essential for evaluation of cough and antitussive therapies. Nonetheless, available algorithms for automatic detection of cough sound have limited sensitivity and the analysis of cough sound often requires ... ...

Abstract	The objective assessment of cough frequency is essential for evaluation of cough and antitussive therapies. Nonetheless, available algorithms for automatic detection of cough sound have limited sensitivity and the analysis of cough sound often requires input from human observers. Therefore, an algorithm for the cough sound detection with high sensitivity would be very useful for development of automatic cough monitors. Here we present a novel algorithm for cough sounds classification based on 8-dimensional numbers octonions and compare it with the algorithm based on standard neural network. The performance was evaluated on a dataset of 5200 cough sounds and 90000 of non-cough sounds generated from the sound recordings in 18 patients with frequent cough caused by various respiratory diseases. Standard classification algorithm had sensitivity 82.2% and specificity 96.4%. In contrast, octonionic classification algorithm had significantly higher sensitivity 96.8% and specificity 98.4%. The use of octonions for classification of cough sounds improved sensitivity and specificity of cough sound detection.
MeSH term(s)	Acoustics ; Adult ; Aged ; Aged, 80 and over ; Cough/diagnosis ; Cough/physiopathology ; Diagnosis, Computer-Assisted/methods ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic/methods ; Neural Networks (Computer) ; Sensitivity and Specificity
Language	English
Publishing date	2018-03-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2077867-3
ISSN	1878-1519 ; 1569-9048
ISSN (online)	1878-1519
ISSN	1569-9048
DOI	10.1016/j.resp.2018.03.010
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Article ; Online: Blocking voltage-gated sodium channels as a strategy to suppress pathological cough.

Sun, Hui / Kollarik, Marian / Undem, Bradley J

Pulmonary pharmacology & therapeutics

2017 Volume 47, Page(s) 38–41

Abstract: Pathological cough is thought to be secondary to inappropriate activation of vagal sensory nerves. Sensory nerves can be activated by a large number of disparate stimuli. The most relevant stimuli to block for effective anti-tussive therapy likely depend ...

Abstract	Pathological cough is thought to be secondary to inappropriate activation of vagal sensory nerves. Sensory nerves can be activated by a large number of disparate stimuli. The most relevant stimuli to block for effective anti-tussive therapy likely depend on the specific underlying pathology that is leading to the coughing. Blocking voltage-gated sodium channels (NaV) will prevent action potential initiation and conduction and therefore prevent sensory communication between the airways and brainstem. In so doing, they would be expected to inhibit evoked cough independently of the nature of the stimulus and underlying pathology. There are nine subtypes of NaVs each with distinct pore-forming alpha subunits referred to NaV1.1-1.9. Among these channels, based on functional and genetic analysis of cough causing vagal afferent nerve subtypes, we hypothesize that targeting NaV1.7 and NaV1.8 is a rational strategy forward for the effective treatment of pathological cough.
MeSH term(s)	Animals ; Antitussive Agents/pharmacology ; Antitussive Agents/therapeutic use ; Cough/drug therapy ; Cough/physiopathology ; Humans ; NAV1.7 Voltage-Gated Sodium Channel/drug effects ; NAV1.7 Voltage-Gated Sodium Channel/metabolism ; NAV1.8 Voltage-Gated Sodium Channel/drug effects ; NAV1.8 Voltage-Gated Sodium Channel/metabolism ; Vagus Nerve/metabolism ; Voltage-Gated Sodium Channel Blockers/pharmacology ; Voltage-Gated Sodium Channel Blockers/therapeutic use ; Voltage-Gated Sodium Channels/drug effects ; Voltage-Gated Sodium Channels/metabolism
Chemical Substances	Antitussive Agents ; NAV1.7 Voltage-Gated Sodium Channel ; NAV1.8 Voltage-Gated Sodium Channel ; Voltage-Gated Sodium Channel Blockers ; Voltage-Gated Sodium Channels
Language	English
Publishing date	2017-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1399707-5
ISSN	1522-9629 ; 1094-5539
ISSN (online)	1522-9629
ISSN	1094-5539
DOI	10.1016/j.pupt.2017.05.010
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Article ; Online: Development of a Mouse Reporter Strain for the Purinergic P2X

Kim, Seol-Hee / Bahia, Parmvir K / Patil, Mayur / Sutton, Sydney / Sowells, Isobel / Hadley, Stephen H / Kollarik, Marian / Taylor-Clark, Thomas E

eNeuro

2020 Volume 7, Issue 4

Abstract: The ATP-sensitive ... ...

Abstract	The ATP-sensitive P2X
MeSH term(s)	Adenosine Triphosphate ; Animals ; Ganglia, Spinal ; Mice ; Neurons ; Neurons, Afferent ; Receptors, Purinergic P2 ; Reflex
Chemical Substances	Receptors, Purinergic P2 ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2020-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0203-20.2020
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Article ; Online: Acidic Pharyngeal Reflux Does Not Correlate with Symptoms and Laryngeal Injury Attributed to Laryngopharyngeal Reflux.

Duricek, Martin / Banovcin, Peter / Halickova, Tatiana / Hyrdel, Rudolf / Kollarik, Marian

Digestive diseases and sciences

2018 Volume 64, Issue 5, Page(s) 1270–1280

Abstract: Background: Laryngopharyngeal reflux (LPR) is suspected when the symptoms are attributed to the penetration of acidic gastroesophageal reflux (GER) into the larynx. However, the relationships between the intensity of LPR and symptoms and laryngeal ... ...

Abstract	Background: Laryngopharyngeal reflux (LPR) is suspected when the symptoms are attributed to the penetration of acidic gastroesophageal reflux (GER) into the larynx. However, the relationships between the intensity of LPR and symptoms and laryngeal injury have not been elucidated. Several factors confound the study of LPR, namely pH is monitored in the pharynx (pharyngeal reflux) but the pharyngeal acidity (pH) required to induce laryngeal injury is unknown, the GER origin of pharyngeal acid is not always established, and a recent treatment with proton pump inhibitors (PPI) confounds the analysis. Aims: We aimed to limit these confounding factors to analyze the relationship between LPR and symptoms and laryngeal injury. Methods: We used dual pharyngeal and distal esophageal 24-h pH/impedance monitoring to establish GER origin of pharyngeal reflux, we used an unbiased approach to analysis by evaluating a whole range of acidity (pH < 6, pH < 5.5, pH < 5.0, pH < 4.5 and pH < 4.0) in patients with suspected LPR without PPI for > 30 days. Results: Pharyngeal reflux was (median[IQR]) 14[8-20.5] and 4[1.5-6.5] pharyngeal reflux episodes with pH < 6.0 and pH < 5.5, respectively. Pharyngeal reflux with pH < 5.0 was rare. Comprehensive analysis did not reveal any correlation between symptoms (reflux symptom index) or laryngeal injury (reflux finding score) and the number of pharyngeal reflux episodes or duration of pharyngeal acid exposure at any pH level. Conclusion: Unbiased comprehensive approach did not reveal any relationship between acidic pharyngeal reflux and the symptoms or laryngeal injury attributed to LPR. Limited clinical usefulness of pharyngeal monitoring reported by others is unlikely due to confounding factors.
MeSH term(s)	Adult ; Female ; Gastroesophageal Reflux/diagnosis ; Gastroesophageal Reflux/physiopathology ; Humans ; Hydrogen-Ion Concentration ; Laryngopharyngeal Reflux/diagnosis ; Laryngopharyngeal Reflux/physiopathology ; Larynx/injuries ; Larynx/physiology ; Male ; Middle Aged ; Pharynx/physiology ; Prospective Studies
Language	English
Publishing date	2018-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	304250-9
ISSN	1573-2568 ; 0163-2116
ISSN (online)	1573-2568
ISSN	0163-2116
DOI	10.1007/s10620-018-5372-1
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