A computational model predicts sex-specific responses to calcium channel blockers in mammalian mesenteric vascular smooth muscle
- Department of Physiology & Membrane Biology, University of California, Davis, United States
- Department of Mathematics, University of California, Davis, United States
- Center for Precision Medicine and Data Sciences, University of California, Davis, United States
Figures
Figure 1
A schematic representation of the Hernandez–Hernandez model.
The components of the model include major ion channel currents shown in purple including the voltage-gated L-type calcium current (ICa), nonselective cation current (INSC), voltage-gated potassium …
Figure 2
Experimentally measured and modeled L-type calcium currents (ICa) from male and female vascular smooth muscle (VSM) cells.
Properties of ICa are derived from measurements in male and female VSM cells isolated from the mouse mesenteric arteries following voltage-clamp steps from –60 to 60 mV in 10 mV steps from a –80 mV …
Figure 3
Experimentally measured and modeled potassium currents (IKvTOT) from male and female vascular smooth muscle cells.
The properties of IKv1.5 and IKv2.1 from experimental measurements in male and female vascular smooth muscle cells isolated from the mouse mesenteric arteries were recorded in response to …
Figure 4
Experimentally measured and modeled large-conductance Ca2+-activated K+ currents (IBKαβ1).
The model was optimized to data from Bao and Cox, 2005. (A) Voltage-dependent activation of IBKαβ1 from experiments performed with three different [Ca]Jun concentrations (1 μM, 10 μM, and 100 μM) …
Figure 5
Membrane potential from experiments and simulations in male and female vascular smooth muscle myocytes.
(A) Whole-cell membrane potential recordings in male and female myocytes showing spontaneous repeat transient hyperpolarization of the membrane potential. (B) Simulated whole-cell membrane potential …
Figure 6
Differential effects of voltage-gated potassium current (IKVTOT) block in male and female myocytes.
(A) Simulated time course of male IKv2.1 (top panel, solid traces) and IKv1.5 (lower panel, dashed traces) at three different baseline membrane potentials (–45 mV green, –40 mV blue, and –35 mV …
Figure 7
Simulated L-type calcium currents (ICa) and calcium influx in male and female vascular smooth muscle cells.
(A) Male and female whole-cell ICa membrane potential relationship. (B) Male and female intracellular calcium concentration in the cytosolic compartment at indicated membrane potential. (C) Time …
Figure 8
A one-dimensional tissue model representation of vascular smooth muscle cells connected in series.
(A) Uncoupled female vessel simulation showing cell 1, cell 50, and cell 100 at a baseline membrane potential of –35 mV. (B) Uncoupled male vessel simulations showing cell 1, cell 50, and cell 100 …
Figure 9
Experimentally measured and modeled intracellular calcium [Ca]i in male and female vessels and response to clinically used L-type Ca2+ channel blocker.
(A) Intracellular calcium [Ca]i in female (blue symbols, n=3) and male (black symbols, n=5) arteries at intravascular pressures ranging from 20 to 120 mmHg. Simulations showing [Ca]i in the …
