Question

I have read in many sources that ischemia-induced depolarization is due to the opening of ATP-sensitive potassium channels and inactivation of Na/K exchangers [1,2]. However, K-atp channels are inward-rectifiers and their extensive opening should cause extracellular hypokalemia besides the fact that in low [ATP]i during ischemia, Mg++ ions are free (not complexed with ATP), and magnesium ions are outward potassium current blockers (i,e, they increase the rectifying power of k-atp, Kir, K-Ach channels)[3,4]. this would cause extracellular hypokalemic depolarization. What is the source of hyperkalemia then?

Answer 1

During a stroke, the inhibition of ATP synthesis leads to neuronal membrane depolarization and the release of K+ and Na+. The extracellular accumulation of glutamate stimulates ionotropic and metabotropic glutamate receptors, including NMDA receptors, which allows for the entry of Ca2+ ions into neurons. Increased intracellular Ca2+ disrupts neuronal function and can lead to cell death.

Step-by-step explanation:

During a stroke or other ischemic event, the inhibition of ATP synthesis by mitochondria leads to a rapid ATP consumption, causing a neuronal membrane depolarization and the release of K+ and Na+ entry into cells. This depolarization allows for the reversal of glutamate uptake carriers and the exit of glutamate from cells, leading to its accumulation in the extracellular space. The extracellular accumulation of glutamate then stimulates ionotropic and metabotropic glutamate receptors, including NMDA receptors, which allow for the entry of Ca2+ ions into neurons, contributing to excitotoxic damage. This increased intracellular Ca2+ level further disrupts neuronal function and can lead to cell death.