biostudies-literatureMakadia HKNHLBI NIH HHSNIGMS NIH HHS211-23https://www.ebi.ac.uk/biostudies/studies/S-EPMC4286605biostudies-literatureUnknown108(1)We developed a multiscale model to bridge neuropeptide receptor-activated signaling pathway activity with membrane electrophysiology. Typically, the neuromodulation of biochemical signaling and biophysics have been investigated separately in modeling studies. We studied the effects of Angiotensin II (AngII) on neuronal excitability changes mediated by signaling dynamics and downstream phosphorylation of ion channels. Experiments have shown that AngII binding to the AngII receptor type-1 elicits baseline-dependent regulation of cytosolic Ca(2+) signaling. Our model simulations revealed a baseline Ca(2+)-dependent response to AngII receptor type-1 activation by AngII. Consistent with experimental observations, AngII evoked a rise in Ca(2+) when starting at a low baseline Ca(2+) level, and a Biophysical journalMultiscale model of dynamic neuromodulation integrating neuropeptide-induced signaling pathway activity with membrane electrophysiology.PMC4286605R01 GM083108R01 HL111621Vadigepalli RFey DMakadia HKSauter TAnderson WDSchwaber JSfalseMultiscale model of dynamic neuromodulation integrating neuropeptide-induced signaling pathway activity with membrane electrophysiology.We developed a multiscale model to bridge neuropeptide receptor-activated signaling pathway activity with membrane electrophysiology. Typically, the neuromodulation of biochemical signaling and biophysics have been investigated separately in modeling studies. We studied the effects of Angiotensin II (AngII) on neuronal excitability changes mediated by signaling dynamics and downstream phosphorylation of ion channels. Experiments have shown that AngII binding to the AngII receptor type-1 elicits baseline-dependent regulation of cytosolic Ca(2+) signaling. Our model simulations revealed a baseline Ca(2+)-dependent response to AngII receptor type-1 activation by AngII. Consistent with experimental observations, AngII evoked a rise in Ca(2+) when starting at a low baseline Ca(2+) level, and a 2015-01-01T00:00:00Z2015 Jan2026-04-29T11:15:42.538Z2019-03-27T01:42:54ZS-EPMC42866052556486810.1016/j.bpj.2014.11.1851