1,720,981 research outputs found
Electrophysiological Characterization of Calcium-Permeable Channels Using Planar Lipid Bilayer.
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Targeting the Mitochondrial Potassium Channel Kv1.3 to Kill Cancer Cells: Drugs, Strategies, and New Perspectives
No full textRoutes for potassium ions across mitochondrial membranes: A biophysical point of view with special focus on the atp-sensitive k+ channel
Full text linkPotassium ions can cross both the outer and inner mitochondrial membranes by means of multiple routes. A few potassium-permeable ion channels exist in the outer membrane, while in the inner membrane, a multitude of different potassium-selective and potassium-permeable channels mediate K+ uptake into energized mitochondria. In contrast, potassium is exported from the matrix thanks to an H+ /K+ exchanger whose molecular identity is still debated. Among the K+ channels of the inner mitochondrial membrane, the most widely studied is the ATP-dependent potassium channel, whose pharmacological activation protects cells against ischemic damage and neuronal injury. In this review, we briefly summarize and compare the different hypotheses regarding the molecular identity of this patho-physiologically relevant channel, taking into account the electrophysiological characteristics of the proposed components. In addition, we discuss the characteristics of the other channels sharing localization to both the plasma membrane and mitochondria
Mitochondrial Ion Channels of the Inner Membrane and Their Regulation in Cell Death Signaling.
Full text linkMitochondria are bioenergetic organelles with a plethora of fundamental functions ranging from metabolism and ATP production to modulation of signaling events leading to cell survival or cell death. Ion channels located in the outer and inner mitochondrial membranes critically control mitochondrial function and, as a consequence, also cell fate. Opening or closure of mitochondrial ion channels allow the fine-tuning of mitochondrial membrane potential, ROS production, and function of the respiratory chain complexes. In this review, we critically discuss the intracellular regulatory factors that affect channel activity in the inner membrane of mitochondria and, indirectly, contribute to cell death. These factors include various ligands, kinases, second messengers, and lipids. Comprehension of mitochondrial ion channels regulation in cell death pathways might reveal new therapeutic targets in mitochondria-linked pathologies like cancer, ischemia, reperfusion injury, and neurological disorders
Intermediate Conductance Calcium-Dependent Potassium Channel (KCa3.1) Interacting Proteins Using Turboid-Based Proximity Labeling Technology: Insights Into Interactome and Related Signaling Pathways in Pancreatic Tumors
No full textFrom channels to canonical wnt signaling: A pathological perspective
Full text linkWnt signaling is an important pathway mainly active during embryonic development and controlling cell proliferation. This regulatory pathway is aberrantly activated in several human diseases. Ion channels are known modulators of several important cellular functions ranging from the tuning of the membrane potential to modulation of intracellular pathways, in particular the influence of ion channels in Wnt signaling regulation has been widely investigated. This review will discuss the known links between ion channels and canonical Wnt signaling, focusing on their possible roles in human metabolic diseases, neurological disorders, and cancer
Mitochondrial K+ channels and their implications for disease mechanisms
No full textThe field of mitochondrial ion channels underwent a rapid development during the last decade, thanks to the molecular identification of some of the nuclear-encoded organelle channels and to advances in strategies allowing specific pharmacological targeting of these proteins. Thereby, genetic tools and specific drugs aided definition of the relevance of several mitochondrial channels both in physiological as well as pathological conditions. Unfortunately, in the case of mitochondrial K+ channels, efforts of genetic manipulation provided only limited results, due to their dual localization to mitochondria and to plasma membrane in most cases. Although the impact of mitochondrial K+ channels on human diseases is still far from being genuinely understood, pre-clinical data strongly argue for their substantial role in the context of several pathologies, including cardiovascular and neurodegenerative diseases as well as cancer. Importantly, these channels are druggable targets, and their in-depth investigation could thus pave the way to the development of innovative small molecules with huge therapeutic potential. In the present review we summarize the available experimental evidence that mechanistically link mitochondrial potassium channels to the above pathologies and underline the possibility of exploiting them for therapy
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