{
  "abstract": "Calcium (Ca2+) signaling is essential for neurotransmitter release, synaptic plasticity, gene expression, and neuronal excitability. Nicotine, the addictive component of tobacco, activates nicotinic acetylcholine receptors (nAChRs), including α4β2- and α7-containing receptor subtypes, thereby altering neuronal Ca2+ entry. ATP2B2 encodes plasma membrane calcium-transporting ATPase 2 (PMCA2), a neuronal high-affinity Ca2+ extrusion pump that helps shape local Ca2+ microdomains. Published work has shown that PMCA2 functionally associates with α7-nicotinic acetylcholine receptors (α7-nAChRs) through postsynaptic density protein 95 (PSD-95) and can influence α7-nAChR surface expression. Genetic and transcriptomic studies have also linked ATP2B2-related pathways to substance use phenotypes, but there is no direct evidence that chronic nicotine alters PMCA2 expression. This narrative review distinguishes established findings from indirect evidence and untested predictions. We propose a mechanistic hypothesis in which chronic nicotine exposure may establish a new calcium-homeostatic equilibrium characterized by α7-nAChR downregulation and compensatory PMCA2 upregulation. We also hypothesize that, during early withdrawal, persistently elevated PMCA2 activity could contribute to excessive Ca2+ extrusion, reduced presynaptic glutamate release, cognitive impairment, and relapse vulnerability. These predicted effects require direct testing in nicotine exposure and withdrawal models. This review aims to examine the roles of calcium signaling and homeostasis in nicotine addiction, with particular emphasis on ATP2B2, which encodes the calcium ion pump PMCA2, and α7-nAChR.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychiatry, Fundamental and Clinical Research on Mental Disorders, Key Laboratory of Luzhou, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, PR China",
    "Zigong Affiliated Hospital of Southwest Medical University & Zigong Institute of Brain Science, Zigong, Sichuan, PR China"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Tingting Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuemei Liang"
    },
    {
      "affs": [
        0
      ],
      "name": "Bo Xiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lanyang Gao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kezhi Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/09pyjb0bz6bmj.bib",
  "cited_by": 0,
  "doi": "10.12659/msm.954223",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13729689/",
  "id": "09pyjb0bz6bmj",
  "issns": [
    "1234-1010",
    "1643-3750"
  ],
  "landing_url": "https://doi.org/10.12659/msm.954223",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Review Articles"
    ],
    [
      "openalex",
      "1312|Nicotinic Acetylcholine Receptors Study"
    ]
  ],
  "openalex": "W7204765049",
  "pdf_url": "https://medscimonit.com/download/inPress/idArt/954223",
  "pmcid": "PMC13729689",
  "pmid": "42952109",
  "published": "2026-10-29",
  "publisher": "International Scientific Information, Inc.",
  "ris": "https://research.draconitic.com/paper/09pyjb0bz6bmj.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:22:27Z",
      "native_id": "PMC13729689",
      "source": "pmc",
      "url": "https://doi.org/10.12659/msm.954223"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Nicotinic Acetylcholine Receptors Study",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A Review of the Roles of Calcium Signaling and Homeostasis in Nicotine Addiction: A Mechanistic Hypothesis Involving ATP2B2/PMCA2 and α7-Nicotinic Acetylcholine Receptors",
  "title_text": "A Review of the Roles of Calcium Signaling and Homeostasis in Nicotine Addiction: A Mechanistic Hypothesis Involving ATP2B2/PMCA2 and α7-Nicotinic Acetylcholine Receptors",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:27Z",
  "url": "https://research.draconitic.com/paper/09pyjb0bz6bmj",
  "venue": "Medical Science Monitor: International Medical Journal of Experimental and Clinical Research",
  "versions": []
}