作者
Josefina Ines del Marmol
发表日期
2016
简介
Mechanosensation is arguably the least understood of all senses. For most physiological processes, the first response to membrane stress is thought to be the opening or closing of mechanosensitive channels 1, but the clonal nature of the first mechanotransducers is still largely unknown. The objective of my research was to identify molecules involved in mechanosensory transduction by both studying known channels as well as performing screens to identify previously uncharacterized channels. Shortly before my research began, Daniel Schmidt from the MacKinnon Lab showed that certain voltage gated potassium channels, not previously associated with mechanosensation, are in fact remarkably sensitive to membrane tension in isolated membrane patches 2. I therefore began investigating the possibility of voltage gated potassium channels being mechanosensitive in physiological contexts. Results using hypo-osmotic swelling provided additional support that Paddle Chimaera and Kv2. 1 are indeed mechanosensitive in cellular contexts 3. Given the close structural similarity between voltage gated potassium channels and other ion channel families, I extended these studies to include sodium and calcium selective voltage gated ion channels using patch inflation, swelling, poking, and stretching. However the sodium selective voltage gated channel, Nav1. 7, and calcium selective voltage gated channels, Cav1. 2 and Cav1. 3, were not found to display major mechanosensitive properties. In a complimentary approach, I performed a screen of 10 different cell lines using the poking assay to identify novel molecules involved in mechanical …
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