title: Evidence for role of acid-sensing ion channels in nucleus ambiguus neurons: essential differences in anesthetized versus awake rats.
abstract: Acid-sensing ion channels (ASIC) are widely expressed in several brain regions including medulla; their role in physiology and pathophysiology is incompletely understood. We examined the effect of acidic pH of 6.2 on the medullary neurons involved in parasympathetic cardiac control. Our results indicate that retrogradely labeled cardiac vagal neurons of nucleus ambiguus are depolarized by acidic pH. In addition, acidic saline of pH 6.2 increases cytosolic Ca(2+) concentration by promoting Ca(2+) influx in nucleus ambiguus neurons. In vivo studies indicate that microinjection of acidic artificial cerebrospinal fluid (pH 6.2) into the nucleus ambiguus decreases the heart rate in conscious rats, whereas it has no effect in anesthetized animals. Pretreatment with either amiloride or benzamil, two widely used ASIC blockers, abolishes both the in vitro and in vivo effects elicited by pH 6.2. Our findings support a critical role for ASIC in modulation of cardiac vagal tone and provide a potential mechanism for acidosis-induced bradycardia, while identifying important differences in the response to acidic pH between anesthetized and conscious rats.
authors.affiliation: Department of Pharmaceutical Sciences, Thomas Jefferson University, Jefferson School of Pharmacy, Philadelphia, PA, 19107, USA.
authors.forename: G Cristina
authors.initials: GC
authors.lastname: Brailoiu
authors.forename: Elena
authors.initials: E
authors.lastname: Deliu
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Altmann
authors.forename: Vineet
authors.initials: V
authors.lastname: Chitravanshi
authors.forename: Eugen
authors.initials: E
authors.lastname: Brailoiu
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000704:Analysis of Variance; D000758:Anesthesia; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005453:Fluorescence; D006321:Heart / Q000294:innervation* / Q000502:physiology; D006339:Heart Rate; D006863:Hydrogen-Ion Concentration; D007530:Isoflurane; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology* / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008845:Microinjections; D009474:Neurons / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D062565:Acid Sensing Ion Channels; D007530:Isoflurane; D002118:Calcium
references.citation: Anesthesiology. 2004 May;100(5):1198-205
references.pmid: 15114218
references.citation: Annu Rev Physiol. 2000;62:573-94
references.pmid: 10845103
references.citation: J Biol Chem. 2009 Nov 13;284(46):31851-9
references.pmid: 19778905
references.citation: Neuron. 2009 Dec 24;64(6):885-97
references.pmid: 20064394
references.citation: Philos Trans R Soc Lond B Biol Sci. 2009 Sep 12;364(1529):2603-10
references.pmid: 19651660
references.citation: Exp Physiol. 2013 Mar;98(3):679-91
references.pmid: 23104934
references.citation: Curr Drug Targets. 2012 Feb;13(2):263-71
references.pmid: 22204324
references.citation: Respir Physiol. 2000 Sep;122(2-3):223-35
references.pmid: 10967346
references.citation: Neuropharmacology. 2003 Apr;44(5):662-71
references.pmid: 12668052
references.citation: J Pharmacol Exp Ther. 2010 Feb;332(2):549-53
references.pmid: 19906780
references.citation: Mol Neurobiol. 2011 Dec;44(3):350-8
references.pmid: 21932071
references.citation: J Membr Biol. 1988 Oct;105(1):1-21
references.pmid: 2852254
references.citation: Science. 1988 Apr 8;240(4849):213-5
references.pmid: 2451291
references.citation: Nature. 1997 Mar 13;386(6621):173-7
references.pmid: 9062189
references.citation: Seizure. 2006 Jul;15(5):275-87
references.pmid: 16549370
references.citation: Seizure. 2001 Jun;10(4):269-78
references.pmid: 11466023
references.citation: Neuroscience. 2003;116(2):573-82
references.pmid: 12559112
references.citation: J Neurophysiol. 2006 Jun;95(6):3865-74
references.pmid: 16510775
references.citation: Nat Neurosci. 2005 Aug;8(8):988-90
references.pmid: 16007081
references.citation: Nature. 1998 Jul 9;394(6689):192-5
references.pmid: 9671304
references.citation: Am J Physiol. 1997 Jul;273(1 Pt 2):R433-41
references.pmid: 9249582
references.citation: J Biol Chem. 2007 Jun 15;282(24):17325-9
references.pmid: 17430882
references.citation: Brain Res. 2003 Jul 11;977(2):247-60
references.pmid: 12834885
references.citation: Am J Physiol Regul Integr Comp Physiol. 2012 Nov 15;303(10):R1023-30
references.pmid: 23019211
references.citation: Anesth Analg. 1999 Jul;89(1):225-9
references.pmid: 10389809
references.citation: J Physiol. 2013 Sep 1;591(17):4223-35
references.pmid: 23878371
references.citation: J Biol Chem. 2004 Mar 19;279(12):11006-15
references.pmid: 14701823
references.citation: Biochim Biophys Acta. 1984 Apr 11;771(2):208-16
references.pmid: 6704395
references.citation: Minerva Anestesiol. 2009 May;75(5):339-44
references.pmid: 19412155
references.citation: J Biol Chem. 1985 Mar 25;260(6):3440-50
references.pmid: 3838314
references.citation: J Neurophysiol. 2008 Mar;99(3):1394-407
references.pmid: 18199815
references.citation: Ann Emerg Med. 1985 Aug;14(8):770-6
references.pmid: 3927794
references.citation: J Biol Chem. 1996 Apr 5;271(14):7879-82
references.pmid: 8626462
references.citation: Anesthesiology. 1994 Jul;81(1):104-16
references.pmid: 8042778
references.citation: J Neurosci Methods. 2001 May 30;107(1-2):47-61
references.pmid: 11389941
references.citation: Anesth Analg. 2009 Jan;108(1):142-8
references.pmid: 19095842
references.citation: Neuron. 2002 Apr 25;34(3):463-77
references.pmid: 11988176
references.citation: Minerva Anestesiol. 2011 Feb;77(2):142-6
references.pmid: 21150849
references.citation: Genes Brain Behav. 2010 Aug;9(6):603-14
references.pmid: 20497234
references.citation: J Physiol. 2012 Oct 1;590(19):4761-75
references.pmid: 22890703
references.citation: Physiol Rev. 2002 Jul;82(3):735-67
references.pmid: 12087134
references.citation: Am J Physiol. 1998 Oct;275(4):R1152-63
references.pmid: 9756546
references.citation: J Biol Chem. 1990 Mar 5;265(7):3763-71
references.pmid: 2154487
references.citation: Auton Neurosci. 2009 Dec 3;151(2):98-105
references.pmid: 19651541
references.citation: J Biol Chem. 1997 Aug 22;272(34):20975-8
references.pmid: 9261094
references.citation: Pharmacol Ther. 2012 May;134(2):127-38
references.pmid: 22233754
references.citation: Nat Rev Neurosci. 2013 Jul;14(7):461-71
references.pmid: 23783197
references.citation: J Neurochem. 2014 May;129(4):628-36
references.pmid: 24521102
references.citation: Am J Emerg Med. 2013 Jan;31(1):271.e5-7
references.pmid: 22809772
references.citation: J Neurochem. 2013 Sep;126(6):739-48
references.pmid: 23795642