2013
Volume 13, Number 1, pp. 12–17
Involvement of potassium channel in AQP1-mediated water and gas transport in erythrocytes
Siddhartha G. Jena
Harvard College, Cambridge, Massachusetts, USA
Diet, lifestyle, and genetics contribute to a staggering 100 million people, nearly a third of the population, suffering from elevated blood cholesterol levels in the USA. Though cholesterol is essential for numerous physiological functions, it is well documented that the long-term effects of elevated levels of plasma cholesterol pose a significant health risk and are causal factors for diseases including angina, cardiovascular disorders and diabetes, resulting in more deaths than cancer and HIV combined. The short-term effect of elevated plasma cholesterol is, however, little known. Our earlier studies report that elevated plasma membrane cholesterol is detrimental to water and CO2 transport in erythrocytes or red blood cells (RBC), and that this transport is mediated via the water channel AQP1. In the current study, the dysfunction of active water and CO2 transport via the AQP1 channel through the RBC membrane is further confirmed. Since the K+ channel is known to interact with AQP1, involvement of the K+ channel and other components associated with AQP1 at the RBC membrane was further explored. Results from the study demonstrate that vH-ATPase, the Cl– channel and the K+ channel are associated with and regulate AQP1 function at the RBC membrane, and that the chloride channel precedes the potassium channel in the AQP1-regulating signalling cascade. Furthermore, the K+ channel inhibitor Glyburide, currently in use to treat Type 2 diabetes, is capable of reversing the detrimental effects of elevated plasma membrane cholesterol on RBC function, suggesting its potential use in therapy.
Keywords: AQP1, erythrocyte, cholesterol, Glyburide, K+ channel