Prenatal Nicotine Exposure Alters the Types of Nicotinic Receptors That Facilitate Excitatory Inputs to Cardiac Vagal Neurons

• Published in: Journal of neurophysiology 2004-10, Vol.92 (4), p.2548-2554
• Main Authors: Huang, Zheng-Gui, Wang, Xin, Evans, Cory, Gold, Allison, Bouairi, Evguenia, Mendelowitz, David
• Format: Article
• Language: English
• Subjects: alpha7 Nicotinic Acetylcholine Receptor; Animals; Bungarotoxins - pharmacology; Cholinesterase Inhibitors - pharmacology; Electric Stimulation; Electrophysiology; Excitatory Postsynaptic Potentials - drug effects; Female; Glutamic Acid - physiology; Heart - growth & development; Heart - innervation; Neostigmine - pharmacology; Neurons - physiology; Nicotine - pharmacology; Nicotinic Agonists - pharmacology; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - physiology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; Vagus Nerve - cytology; Vagus Nerve - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00500.2004

Department of Pharmacology and Physiology, George Washington University, Washington, DC 20037 Submitted 12 May 2004; accepted in final form 19 June 2004 Nicotinic receptors play an important role in modulating the activity of parasympathetic cardiac vagal neurons in the medulla. Previous work has shown nicotine acts via at least three mechanisms to excite brain stem premotor cardiac vagal neurons. Nicotine evokes a direct increase in holding current and facilitates both the frequency and amplitude of glutamatergic neurotransmission to cardiac vagal neurons. This study tests whether these nicotinic receptor–mediated responses are endogenously active, whether 4 2 and 7 nicotinic receptors are involved, and whether prenatal exposure to nicotine alters the magnitude of these responses and the types of nicotinic receptors involved. Application of neostigmine (10 µM) significantly increased the holding current, amplitude, and frequency of miniature excitatory postsynaptic current (mEPSC) glutamatergic events in cardiac vagal neurons. In unexposed animals, the nicotine-evoked facilitation of mEPSC frequency, but not mEPSC amplitude or holding current, was blocked by -bungarotoxin (100 nM). Prenatal nicotine exposure significantly exaggerated and altered the types of nicotinic receptors involved in these responses. In prenatal nicotine-exposed animals, -bungarotoxin only partially reduced the increase in mEPSC frequency. In addition, in prenatal nicotine-exposed animals, the increase in holding current was partially dependent on -7 subunit–containing nicotinic receptors, in contrast to unexposed animals in which -bungarotoxin had no effect. These results indicate prenatal nicotine exposure, one of the highest risk factors for sudden infant death syndrome (SIDS), exaggerates the responses and changes the types of nicotinic receptors involved in exciting premotor cardiac vagal neurons. These alterations could be responsible for the pronounced bradycardia that occurs during apnea in SIDS victims. Address for reprint requests and other correspondence: D. Mendelowitz, Dept. of Pharmacology and Physiology, George Washington Univ., 2300 Eye St N.W., Washington, DC 20037 (E-mail: dmendel{at}gwu.edu ).