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Cerebral artery diameter is regulated by calcium influx via voltage\u2010gated L\u2010type Ca\n V<\/jats:sub>\n 1.2 channels, which contribute to arterial myocyte contractility. The potential effects of A\u03b2 on vascular Ca\n V<\/jats:sub>\n 1.2 channels remain unclear. To address this knowledge gap, we test the hypothesis that A\u03b2 alters vascular Ca\n V<\/jats:sub>\n 1.2 channel spatiotemporal properties. Using freshly dissected cerebral arteries and arterial myocytes from wild\u2010type (WT) mice, super\u2010resolution imaging revealed that A\u03b2\n 1\u201042<\/jats:sub>\n , but not A\u03b2\n 1\u201040<\/jats:sub>\n , increased the clustering of Ca\n V<\/jats:sub>\n 1.2 channels in male but not female or ovariectomized female arterial myocytes. This A\u03b2\n 1\u201042<\/jats:sub>\n \u2010associated Ca\n V<\/jats:sub>\n 1.2 clustering appears to depend on NADPH oxidases, protein kinase C and protein kinase A signalling. Studies using male arterial myocytes from S1928A knockin mice suggested that A\u03b2\n 1\u201042<\/jats:sub>\n effects on Ca\n V<\/jats:sub>\n 1.2 clustering require phosphorylation of the \u03b11\n C<\/jats:sub>\n \/Ca\n V<\/jats:sub>\n 1.2 pore\u2010forming subunit at serine\u20101928. Single\u2010channel electrophysiology showed increased Ca\n V<\/jats:sub>\n 1.2 channel activity and cooperative gating in WT male arterial myocytes exposed to A\u03b2\n 1\u201042<\/jats:sub>\n , but not in female WT or male S1928A myocytes. In functional studies, WT, but not S1928A, cerebral arteries acutely incubated with A\u03b2\n 1\u201042<\/jats:sub>\n demonstrated enhanced constriction in response to the Ca\n V<\/jats:sub>\n 1.2 channel agonist BayK8644. These findings provide insight into mechanisms by which A\u03b2 may influence Ca\n V<\/jats:sub>\n 1.2 properties and vascular contractility, potentially contributing to vascular changes in Alzheimer's disease.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Specific amyloid\u2010\u03b2 peptide (A\u03b2\n 1\u201042<\/jats:sub>\n ) induces \u03b11\n C<\/jats:sub>\n \/Ca\n V<\/jats:sub>\n 1.2\u00a0super\u2010clustering in cerebral vascular smooth muscle, enhancing Ca\n V<\/jats:sub>\n 1.2 activity.\n <\/jats:p>\n <\/jats:list-item>\n \n \n A\u03b2\n 1\u201042<\/jats:sub>\n engages distinct pathways involving NOX\u2010derived ROS\u2010activated PKC and PKA (through unknown mechanisms) to drive \u03b11\n C<\/jats:sub>\n \/Ca\n V<\/jats:sub>\n 1.2\u00a0spatiotemporal reorganization leading to enhance cerebral artery contractile responses to Ca\n V<\/jats:sub>\n 1.2 agonists.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The A\u03b2\n 1\u201042<\/jats:sub>\n \u2010mediated PKC\u2010 and PKA\u2010dependent effects on \u03b11\n C<\/jats:sub>\n \/Ca\n V<\/jats:sub>\n 1.2\u00a0spatiotemporal remodelling and cerebral artery contractility require phosphorylation of \u03b11\n C<\/jats:sub>\n at S1928, as the effects are lost in S1928A tissue\/cells.\n <\/jats:p>\n <\/jats:list-item>\n \n \n The molecular and functional changes occur exclusively in male vascular smooth muscle cells, revealing sex\u2010specific vulnerabilities in amyloid \u03b2\u2010related cerebrovascular pathology that are independent of sex hormones and establishing a potential mechanism for vascular dysfunction in conditions with elevated A\u03b2\n 1\u201042<\/jats:sub>\n .\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp289276","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:41:36Z","timestamp":1766155296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Amyloid \u03b2 alters vascular Ca\n V<\/sub>\n 1.2 channel spatiotemporal properties"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-2712","authenticated-orcid":false,"given":"Jade L.","family":"Taylor","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of California Davis Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9399-4013","authenticated-orcid":false,"given":"Miguel Martin\u2010Aragon","family":"Baudel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pereira da Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7960-7531","authenticated-orcid":false,"given":"Johannes W.","family":"Hell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1935-8400","authenticated-orcid":false,"given":"Madeline","family":"Nieves\u2010Cintron","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6864-6594","authenticated-orcid":false,"given":"Manuel F.","family":"Navedo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of California Davis Davis CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"crossref","DOI":"10.1155\/2019\/1050476","article-title":"Amyloid peptide \u03b21\u201042 induces integrin \u03b1IIb\u03b23 activation, platelet adhesion, and thrombus formation in a NADPH oxidase\u2010dependent manner","volume":"2019","author":"Abubaker A. 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