Prenatal exposure to cigarette smoke affects the physiology of pedunculopontine nucleus (PPN) neurons in development

Nicotine Blocks the Hyperpolarization-Activated CurrentIhand Severely Impairs the Oscillatory Behavior of Oriens-Lacunosum Moleculare Interneurons

“…Molecular docking calculations have allowed estimating nicotine putative binding site within the HCN channel pore, in a position close to the one identified for ZD 7288. Based on a previous HCN channel model (Giorgetti et al, 2005) and mutagenesis experiments, Cheng et al (2007) have found that the phenyl ring of ZD 7288 occupies a hydrophobic cavity formed by Ala425 and Ile432. The charged ring aligns with the axis of the inner pore closely corresponding to the localization of the K ϩ ions, observed in the KcsA K ϩ channel crystal structure.…”

“…In particular, in canine ventricular myocytes, nicotine has been shown to reduce the transient outward K ϩ current I A (Wang et al, 2000a) and the inward rectifier potassium current mediated by Kir channels, which in cardiac cells contribute to stabilize the resting membrane potential at relatively negative values and to regulate cell excitability (Wang et al, 2000b). In a previous study aimed at clarifying whether the chronic exposure of pregnant mothers to cigarette smoke affects the intrinsic membrane properties of pedunculopontine nucleus neurons in brainstem slices of the offspring, an increase of I h was detected (Good et al, 2006). It should be stressed however that, in contrast with the present data, in pedunculopontine nucleus neurons, I h was studied without blocking synaptic transmission and/or nAChRs.…”

Off the Beaten Path: Drug Addiction and the Pontine Laterodorsal Tegmentum

“…Similar concentrations of alcohol induced a depolarization via inhibition of an inwardly rectifying potassium conductance in high frequency bursting cells within the striatum; whereas, alcohol had no action on membrane conductances within a third type of striatal neuron [137]. In preliminary studies, we have found that the I H current, which exhibits a developmental expression within the LDT paralleling that seen in cells of the PPT [138], is decreased in cholinergic neurons by acute exposure to nicotine. Almost certainly differential actions of various drugs of abuse on cellular conductances are likely to exist across the heterogeneous LDT neuronal population.…”

Prenatal Nicotine Exposure Selectively Affects Nicotinic Receptor Expression in Primary and Associative Visual Cortices of the Fetal Baboon

“…Thus, the changes observed here would suggest altered cholinergic transmission in the occipital region which may have profound physiological effects [53]. These effects have been shown to persist into the postnatal period [21, 56]. …”

“…They are present in the human brain as early as 4-6 weeks gestation [24], and play a key role in neuronal differentiation and synaptogenesis, as well as neurotransmission [30]. The activation of nAChRs by exogenous nicotine during fetal life has been shown in different experimental paradigms to profoundly affect the development of the neuroanatomical organization of the brain [36], with persistent adverse consequences postnatally [21, 56]. Because the different subtypes of nAChRs are known to have unique distribution patterns, developmental profiles [13], and pharmacological properties [22], their activation by exogenous nicotine is likely to result in complex effects in different regions of the brain and at different stages of development.…”