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Here, we describe an in silico model, which we call the \u2018Hernandez\u2013Hernandez model\u2019, of electrical and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling in arterial myocytes based on new experimental data indicating sex-specific differences in male and female arterial myocytes from murine resistance arteries. The model suggests the fundamental ionic mechanisms underlying membrane potential and intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    signaling during the development of myogenic tone in arterial blood vessels. Although experimental data suggest that K\n                    <jats:sub>V<\/jats:sub>\n                    1.5 channel currents have similar amplitudes, kinetics, and voltage dependencies in male and female myocytes, simulations suggest that the K\n                    <jats:sub>V<\/jats:sub>\n                    1.5 current is the dominant current regulating membrane potential in male myocytes. In female cells, which have larger K\n                    <jats:sub>V<\/jats:sub>\n                    2.1 channel expression and longer time constants for activation than male myocytes, predictions from simulated female myocytes suggest that K\n                    <jats:sub>V<\/jats:sub>\n                    2.1 plays a primary role in the control of membrane potential. Over the physiological range of membrane potentials, the gating of a small number of voltage-gated K\n                    <jats:sup>+<\/jats:sup>\n                    channels and L-type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels are predicted to drive sex-specific differences in intracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and excitability. We also show that in an idealized computational model of a vessel, female arterial smooth muscle exhibits heightened sensitivity to commonly used Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel blockers compared to male. In summary, we present a new model framework to investigate the potential sex-specific impact of antihypertensive drugs.\n                  <\/jats:p>","DOI":"10.7554\/elife.90604","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T15:39:12Z","timestamp":1694533152000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.90604","source":"Crossref","is-referenced-by-count":12,"title":["A computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6940-9005","authenticated-orcid":true,"given":"Gonzalo","family":"Hernandez-Hernandez","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05rrcem69","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Physiology & Membrane Biology, University of California, Davis","place":["Davis, United 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