Title

Physiological roles of gap junction protein pannexin

Date of Award

2007

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Physiology and Biophysics

First Committee Member

Gerhard Dahl, Committee Chair

Abstract

Open, unopposed gap junction hemichannels can be deleterious to a cell due to their large conductance and permeation properties. But brief openings of the hemichannels, triggered by a variety of stimuli, may be of physiological importance for cells. A previous study showed that pannexin 1 hemichannels (pannexons) are mechanosensitive and involved in non-vesicular ATP release from cells. Using different approaches (electrophysiology, dye uptake experiments, immunohistochemistry) in different systems (Xenopus oocytes, human erythrocytes) we show that these gap junction proteins participate with P2Y purinergic receptors in the extracellular mode of calcium wave propagation by releasing ATP from erythrocytes.Pannexin 1 channels are involved in local regulation of blood flow by providing the ATP release channel in erythrocytes. Oxygen-deprived or sheer-stressed erythrocytes release ATP, which binds to purinergic receptors on endothelial cells. This ATP initiates a calcium wave that propagates retrogradely over the endothelium to the precapillary sphincter region, where induces NO production and relaxation of the smooth muscle.Pannexons may also provide the "large pore" formation and release of various active components from cells after ATP stimulation of P2X7 purinergic receptors. Pannexons were experimentally opened by application of ATP to oocytes expressing both P2X7 receptors and pannexin 1.Furthermore, Hirudo medicinalis gap junction proteins innexin 2 and innexin 3 were found to exhibit similar properties with pannexin 1 (with respect of forming non-junctional membrane channels). These channels are also mechanosensitive.

Keywords

Biophysics, General

Link to Full Text

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