The role of KATP channels in cerebral ischemic stroke and diabetes

Abstract

ATP-sensitive potassium (KATP) channels are ubiquitously expressed on the plasma membrane of cells in multiple organs, including the heart, pancreas and brain. KATP channels play important roles in controlling and regulating cellular functions in response to metabolic state, which are inhibited by ATP and activated by Mg-ADP, allowing the cell to couple cellular metabolic state (ATP/ADP ratio) to electrical activity of the cell membrane. KATP channels mediate insulin secretion in pancreatic islet beta cells, and controlling vascular tone. Under pathophysiological conditions, KATP channels play cytoprotective role in cardiac myocytes and neurons during ischemia and/or hypoxia. KATP channel is a hetero-octameric complex, consisting of four pore-forming Kir6.x and four regulatory sulfonylurea receptor SURx subunits. These subunits are differentially expressed in various cell types, thus determining the sensitivity of the cells to specific channel modifiers. Sulfonylurea class of antidiabetic drugs blocks KATP channels, which are neuroprotective in stroke, can be one of the high stoke risk factors for diabetic patients. In this review, we discussed the potential effects of KATP channel blockers when used under pathological conditions related to diabetics and cerebral ischemic stroke.

Increased risk for cerebral ischemic stroke in diabetes: genetically polymorphic CYP mediated production of neuroprotective EETs and sulfonylurea metabolism in relation with KATP channels

“…Cytoprotective role of K ATP channels in brain and heart have been reported previously as mentioned by Szeto et al [1]. EETs produced by the CYP 2J2, 2C8, and 2C9 have been reported to have protective effects [8].…”

“…Szeto et al thoroughly reviewed the role of ATP sensitive potassium (K ATP ) channels in cerebral ischemic stroke and diabetes in a recent article [1]. K ATP channels are expressed in many organs, such as brain, heart, and pancreas.…”

“…K ATP channels are expressed in many organs, such as brain, heart, and pancreas. Recent studies demonstrated the protective role of these channels in cardiac pathologies and ischemia of brain [1]. Diabetic patients are often prescribed with sulfonylurea oral antidiabetics, for which the mechanism of action is inhibition of K ATP channels and thereby, increased excretion of insulin by pancreatic islet cells.…”

Potassium channels in vascular smooth muscle: a pathophysiological and pharmacological perspective

“…Nonetheless, our understanding is lacking about the regional heterogeneity in the nature and composition of K + channels in different vascular beds. Moreover, given strong evidence of the critical role of K + channels in a variety of vascular pathological conditions including hypertension, PA hypertension, atherosclerosis, and diabetes mellitus, targeting K + channel function represents a novel and promising strategy for the prevention and treatment of a variety of diseases . However, many complex alterations in vascular K + channel functions have been described in diseases, and the understanding of the regulation of expression and function of the K + channels in these disease states is also limited, especially since these diseases relate to different vascular beds throughout the body.…”

Nutritional ketosis as an intervention to relieve astrogliosis: Possible therapeutic applications in the treatment of neurodegenerative and neuroprogressive disorders

“…Astrocytic Cx43 gap junctions and pannexin hemichannels are held in an open configuration in a state of chronic neuroinflammation and oxidative stress as a result of the S-nitrosylation and oxidative modification of regulatory cysteine thiol motifs leading to conformational changes and loss of functional plasticity (reviewed by [306,307]). This compromised function not only impairs their role in K + homeostasis but also negatively impairs astrocyte-mediated glutamate uptake and dispersal [308,309].…”