Computational study of selectivity, gating and mutation in the acetylcholine receptor and potassium channels

Funded Activity Summary

One way cells in living organisms communicate with each other is via the passage of charged particles across the cell membrane. This takes place through ion channels, large protein molecules that span the membrane and allow small molecules or ions to pass through a central pore. Malfunction of ion channels is known to underlie a variety of disorders including epilepsy, hypertension, kidney disease, heart attack, deafness. Channels also provide promising targets for making new broad spectrum antibiotics and antivirals. This project aims to study two important types of ion channel: acetylcholine receptors that convey signals between nerve and muscle cells, and potassium channels that regulate the nerve impulses themselves. The binding of the neurotransmitter acetylcholine released from a nerve cell to acetylcholine receptors in the muscle cell prompts the opening of a cation conductive pore. The resulting influx of ions initiates a cascade of events ending in the contraction of the muscle fibre. However, the way in which this channel opening is initiated and how ions move into the muscle cell remain to be determined. Potassium channels are primarily used to rapidly 'switch off' nerve impulses so that subsequent messages can be passed through the nerve cell. To do this they have to be highly discriminatory, allowing only potassium to pass across the cell membrane and not sodium that would initiate another impulse. Although we now know what these tiny proteins look like, it is not clear how they differentiate between types of ions while still allowing many millions to pass each second. We will use computer simulations to study how these two type of channel open and close, and how they discriminate between different ion types. Using sophisticated computational techniques on Australia's most powerful supercomputers we aim to elucidate this fundamental area of human biology in the hope of deriving treatments for some debilitating neuromuscular diseases.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $301,393.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Biological Physics

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

Ion channels | computer simulation | epilepsy | ion channel dysfunction | myasthenia gravis | nervous system disorders | neuromuscular disease | nicotinic receptors | nueromuscular junction | potassium channels

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