- Potassium (K⁺) channels are a diverse and vital group of transmembrane proteins that enable the selective flow of potassium ions across cellular membranes. They are among the most widely distributed ion channels in all living organisms—from bacteria to humans—and play a fundamental role in controlling cell membrane potential, electrical excitability, and ionic homeostasis.
- In excitable cells such as neurons, muscle cells, and endocrine cells, potassium channels are crucial for repolarizing the membrane after action potentials, regulating firing frequency, and shaping signal propagation. In non-excitable cells, they contribute to functions such as cell volume regulation, insulin secretion, and salt and water transport in epithelial tissues.
- Structurally, potassium channels are typically composed of four pore-forming α-subunits, each contributing to a central channel pore. These subunits contain conserved sequences that form a selectivity filter, allowing only K⁺ ions to pass while excluding smaller ions like Na⁺. This remarkable selectivity is achieved through precise coordination of dehydrated K⁺ ions with backbone carbonyl groups within the channel. Depending on the channel type, these α-subunits may function alone or associate with auxiliary subunits that modulate channel behavior, trafficking, and responsiveness to cellular signals. Potassium channels can be categorized into several major families based on their structural features and activation mechanisms, including voltage-gated (Kv), inward rectifiers (Kir), two-pore-domain (K2P), and calcium-activated (KCa) potassium channels.
- Each family of potassium channels serves distinct physiological functions. Voltage-gated K⁺ (Kv) channels open in response to membrane depolarization and are key players in action potential repolarization and frequency adaptation in neurons and cardiomyocytes. Inward rectifier K⁺ (Kir) channels preferentially allow K⁺ to enter the cell and help stabilize the resting membrane potential, particularly in cardiac and smooth muscle cells. Two-pore domain K⁺ (K2P) channels generate background or “leak” currents that influence cellular excitability and respond to a variety of stimuli including pH, stretch, and temperature. Calcium-activated K⁺ (KCa) channels, on the other hand, open in response to rises in intracellular Ca²⁺ levels and are involved in linking calcium signaling to membrane potential regulation, playing a key role in smooth muscle tone, neuronal afterhyperpolarization, and secretion.
- Potassium channels are extensively regulated by intracellular signaling molecules, neurotransmitters, hormones, phosphorylation, and lipid interactions, making them integral to cellular responsiveness and adaptability. Their dysregulation or mutation can lead to a wide array of diseases collectively known as channelopathies. For example, mutations in voltage-gated potassium channels can result in epilepsy, cardiac arrhythmias (such as long QT syndrome), ataxia, and periodic paralysis. Inward rectifier channel mutations are implicated in Andersen-Tawil syndrome and congenital hyperinsulinism, while altered expression or function of K2P channels has been associated with depression, pain disorders, and anesthesia sensitivity. Because of their critical roles, potassium channels are important therapeutic targets, and several drugs—such as antiarrhythmics, anticonvulsants, and bronchodilators—act by modulating K⁺ channel activity.
