Table 1. Summary of inside-out and outside-in signaling during smoking
Outside-in: Activated nAChRs in the plasma membraneInside-out: Chaperoned nAChRs in the ER
Nominal cellular effectsNa+ and Ca2+ influx, increased neuronal excitability, calcium signaling, nAChR desensitizationStabilization of α4β2 subunit combinations, increased nAChR in the plasma membrane, biased subunit composition
EC50 for effect0.3 – 4 µMa (Buisson et al., 1996; Gopalakrishnan et al., 1997; Pacheco et al., 2001; Kuryatov et al., 2005)30 nM (Kuryatov et al., 2005)
Fraction average activation for a typical smoking habitb0.10.7
Hypothesized organismal effectsSense of well-being, cognitive boost, appetite suppression, increased tolerance of stressful stimuli, suppression of withdrawal (Miwa et al., 2011; Naudé et al., 2015; Nees, 2015; Picciotto et al., 2015)Early events of nicotine dependence (Govind et al., 2009; Henderson and Lester, 2015)
Timescale of organismal effectsMinutesDays to weeks
  • a Dependent on subunit composition and assay.

  • b 1 cigarette/hour for 12 h leads to ∼100 nM sustained nicotine concentration.