HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 101/3/1141    most recent 90680.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kamendi, H. W. Articles by Mendelowitz, D. Search for Related Content PubMed PubMed Citation Articles by Kamendi, H. W. Articles by Mendelowitz, D.

Abolishment of Serotonergic Neurotransmission to Cardiac Vagal Neurons During and After Hypoxia and Hypercapnia With Prenatal Nicotine Exposure

¹Department of Pharmacology and Physiology, The George Washington University, Washington, DC; and ²Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah

Submitted 13 June 2008; accepted in final form 15 December 2008

Abstract

Cardioinhibitory cardiac vagal neurons (CVNs) do not receive inspiratory-related excitatory inputs under normal conditions. However, excitatory purinergic and serotonergic pathways are recruited during inspiratory activity after episodes of hypoxia and hypercapnia (H/H). Prenatal nicotine (PNN) exposure is known to dramatically change cardiorespiratory responses and decrease the ability to resuscitate from H/H. This study tested whether PNN exposure alters excitatory neurotransmission to CVNs in the nucleus ambiguus during and after H/H. Spontaneous and inspiratory evoked excitatory postsynaptic currents were recorded in CVNs from rats that were exposed to nicotine (6 mg·kg^–1·d^–1) throughout the prenatal period. In contrast to unexposed animals, in PNN animals H/H recruited excitatory neurotransmission to CVNs during inspiratory-related activity that was blocked by the 3β4 nicotinic acetylcholine receptor (nAChR) blocker -conotoxin AuIB (-CTX AuIB, 100 µM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 50 µM) and D(–)-2-amino-5-phosphonopentanoic acid (AP5, 50 µM), selective AMPA/kainate and N-methyl-D-aspartate receptor blockers, respectively. Following H/H, there was a significant increase in inspiratory-related excitatory postsynaptic currents that were unaltered by -CTX AuIB or ondansetron, a 5-HT3 receptor blocker, but were subsequently inhibited by pyridoxalphosphate-6-azophenyl-2', 4'-disulphonic acid (100 µM), a purinergic receptor blocker and CNQX and AP5. The results from this study demonstrate that with PNN exposure, an excitatory neurotransmission to CVNs is recruited during H/H that is glutamatergic and dependent on activation of 3β4-containing nAChRs. Furthermore, exposure to PNN abolishes a serotonergic long-lasting inspiratory-related excitation of CVNs that is replaced by recruitment of a glutamatergic pathway to CVNs post H/H.