Heart Wall - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 311

The heart adapts to changes in diet and stress by regulating metabolism and gene
expression to maximize energy efficiency. The heart regulates energy homeostasis,
i.e., the balance between energy consumption and expenditure, via heart-specific
Med13, a regulatory subunit of the Mediator complex, which controls transcription
by nuclear hormone receptors, especially NR1a1 and NR1a2, 54 in addition to other
nuclear receptors, such as NR2b1 to NR2b3 and NR1c3, as well as well as their
coactivators and corepressors, such as NCoR1 and SREBP proteins [ 597 ].
Cardiac expression of Med13 is inhibited by a heart-specific microRNA,
miR208a [ 597 ]. 55 In mice, overexpression of Med13 or inhibition of miR208a
confers resistance to high-fat diet-induced obesity and improves insulin sensitivity
and glucose tolerance. Subunit Med13 enhances the body's metabolism and causes
an increased energy expenditure, as, although food intake remains normal, oxygen
consumption and carbon dioxide production rise. Conversely, in the absence of
cardiac Med13 activity, lipids accumulate without changes in food intake. Changes
in energy consumption can affect thermogenesis.

6.4 Main Ion Currents

Efficient cyclic heartbeat is achieved by fast and brief contraction followed by a
rapid and short-duration relaxation triggered by quick Ca 2 + ions flux in and out the
cytosol of cardiomyocytes, that enables blood ejection from ventricules and venous
blood admission in cardiac chambers.
Activated ion channels generates ion fluxes (Table 6.10 ) in and out nodal cells
and cardiomyocytes. Ionic currents and resulting action potentials vary among
mammal species, and within an animal species, cell types.
Mathematical models of ion fluxes across the plasma and organelle membranes
of nodal cells or cardiomyocytes as well as ion motions and sequestration within
the cytosol and certain organelles are aimed at restoring the conduction velocity and
action potential duration of the explored region of the heart wall.
In the heart, MinK-related peptide MiRP1 is an auxiliary subunit of K V 11.1
responsible for the rapid delayed rectifier K + current ( i K , r ). It modulates ionic flux
amplitude via channel conductance and/or gating kinetics. It also influences K V 11.1
stability. Upon phosphorylation (Ser98), it accelerates K V 11.1 degradation [ 598 ].
Its density is higher in ventricles than in atria in spontaneously hypertensive rat and
guinea pig hearts. Mutations in the KCNE2 gene that encodes MiRP1 can cause
long QT syndrome (LQT6).
Adaptive and maladaptive cardiac hypertrophy is associated with a change in
density of potassium channels. In maladaptive hypertrophy in humans, angiotensin-
2 or endothelin-1 reduces abundance of K V 4.3 that is responsible for the transient

54 Thyroid hormones regulate the metabolic rate, energy expenditure, and cardiac contractility.
55 MicroRNA-208A is encoded by an intron of the cardiac-specific

α

-myosin heavy-chain gene.