Post-transcriptional control of type 2 inositol 1,4,5-trisphosphate receptor (InsP3R2) by microRNA during cardiac hypertrophy

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The beating of the heart as it pumps blood around the body is induced by an increase in the amount of calcium in its muscle cells. This increase in calcium is brought about through the entry of calcium into the cell from the extracellular space, which then causes release of calcium from calcium stores in the cell. The movement of calcium within the cell occurs through channel proteins, which span the outer membrane of the cell and the membranes that bound the intracellular calcium stores. Following the induction of contraction of the cardiac muscle cells, relaxation is then brought about by the action of energy consuming pumps, which transport calcium back into the stores and out of the cell. This project focuses upon the regulation of expression of an intracellular calcium channel called the IP3R in the muscle cells of the heart that plays a relatively minor role in regulation of contraction in the young healthy heart. With the onset of disease or ageing, the abundance of this channel is increased causing extra calcium increases in the cell, which may induce arrhythmias or inappropriate cardiac growth. Both of these effects can lead to heart failure and death. The mechanism by which we consider that the expression of the IP3R is regulated is through a small fragment of RNA called a microRNA. Our preliminary evidence suggests that the amount of this microRNA is decreased by calcium release from the IP3R. Due to the decrease in the microRNA, which normally suppresses IP3R expression, IP3R expression is allowed to increase. As such, it appears that the IP3R controls its own abundance through calcium and microRNA abundance.

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