Prenatal nicotine exposure alters the types of nicotinic receptors that facilitate excitatory inputs to cardiac vagal neurons.
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 alpha4beta2 and alpha7 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 microM) 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 alpha-bungarotoxin (100 nM). Prenatal nicotine exposure significantly exaggerated and altered the types of nicotinic receptors involved in these responses. In prenatal nicotine-exposed animals, alpha-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 alpha-7 subunit-containing nicotinic receptors, in contrast to unexposed animals in which alpha-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.
Huang
Zheng-Gui
ZG
Dept. of Pharmacology and Physiology, George Washington Univ., 2300 Eye St N.W., Washington, DC 20037, USA.
Wang
Xin
X
Evans
Cory
C
Gold
Allison
A
Bouairi
Evguenia
E
Mendelowitz
David
D
D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000502:physiology; D006321:Heart / Q000254:growth & development / Q000294:innervation*; D009388:Neostigmine / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; D002800:Cholinesterase Inhibitors; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D009388:Neostigmine; D018698:Glutamic Acid; D009538:Nicotine