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Simple Summary: Epithelial Sodium Channel (ENaC) is a renal ion channel responsible for a major fraction of total body sodium balance. MARCKS-like Protein-1 (MLP-1) is a membrane protein that controls the distribution of membrane phosphatidylinositol 4, 5-bisphosphate (PIP2). PIP2 strongly activates ENaC with a half-activating concentration of 21 ± 1.17 μM. Normal channel activity requires MLP-1 associated with the inner leaflet of the cell membrane. MLP-1′s strongly positively charged effector domain sequesters PIP2 electrostatically and increases the local concentration of PIP2 over a hundred-fold. By controlling local PIP2 concentration, MLP-1 controls ENaC activity and, consequently, total body sodium balance. We examined the interaction of a membrane-associated protein, MARCKS-like Protein-1 (MLP-1), and an ion channel, Epithelial Sodium Channel (ENaC), with the anionic lipid, phosphatidylinositol 4, 5-bisphosphate (PIP2). We found that PIP2 strongly activates ENaC in excised, inside-out patches with a half-activating concentration of 21 ± 1.17 µM. We have identified 2 PIP2 binding sites in the N-terminus of ENaC β and γ with a high concentration of basic residues. Normal channel activity requires MLP-1's strongly positively charged effector domain to electrostatically sequester most of the membrane PIP2 and increase the local concentration of PIP2. Our previous data showed that ENaC covalently binds MLP-1 so PIP2 bound to MLP-1 would be near PIP2 binding sites on the cytosolic N terminal regions of ENaC. We have modified the charge structure of the PIP2 –binding domains of MLP-1 and ENaC and showed that the changes affect membrane localization and ENaC activity in a way consistent with electrostatic theory. [ABSTRACT FROM AUTHOR]

Research shows that the embryonic ventricular diastolic and systolic function in three-week old chick embryos is not affected by acute ventricular outflow tract occlusion. Experiments designed to measure ventricular-vascular dynamic coupling measurements using white Leghorn chicken eggs are described. Ventricular contractile reserver calculations are shown.

Developmental alterations in wave-propagation velocity (WPV) were determined by measuring both wave-front and phase velocities in chick embryos at stages 18-24 and correlated the results to other hemodynamic parameters by acute changes in the volume of circulating blood. Phase velocity was calculated employing fourier transform up to fourth harmonics while wave-front velocity was measured by threshold technique. It was observed that developmental changes in WPV were associated with the size of the vascular system, elastic elements and pressure range of the arterial wall in vasculogenesis.

It is possible to use lumped parameter circuit models to describe the embryonic and mature vascular systems. Researchers have been able to evaluate the accuracy of 18 different analog circuit models to describe embryonic arterial impedance within the restrictions of the existing measurement system. The most satisfactory representations of embryonic arterial load were achieved with the adaptation of the traditional three-element windkessel model to include a proximal inductance term.

The embryonic vascular system responds to changes in the volume of circulating blood by maintaining constant blood pressure levels. The artificial reduction of blood circulation increases the peripheral resistance of the blood vessels and produces constant levels of hydraulic pressure. This reaction is due to the efficient utilization of energy necessary for vascular development in the embryonic vasculatory system. The embryonic vasculature is also regulated by vasoactivators in the absence of autonomic control.