The Ca²⁺ ion is used ubiquitously as an intracellular signaling molecule due to its high external and low internal concentration. Many Ca²⁺-sensing ion channel proteins have evolved to receive and propagate Ca²⁺ signals. Among them are the Ca²⁺-activated potassium channels, a large family of potassium channels activated by rises in cytosolic calcium in response to Ca²⁺ influx via Ca²⁺-permeable channels that open during the action potential or Ca²⁺ release from the endoplasmic reticulum. The Ca²⁺ sensitivity of these channels allows internal Ca²⁺ to regulate the electrical activity of the cell membrane. Activating these potassium channels controls many physiological processes, from the firing properties of neurons to the control of transmitter release. This review will discuss what is understood about the Ca²⁺ sensitivity of the two best-studied groups of Ca²⁺-sensitive potassium channels: large-conductance Ca²⁺-activated K⁺ channels, K_Ca1.1, and small/intermediate-conductance Ca²⁺-activated K⁺ channels, K_Ca2.x/K_Ca3.1.

Small-conductance Ca²⁺-activated K⁺ (K_Ca2.1-K_Ca2.3) channels modulate neuronal and cardiac excitability. We report cryo-electron microscopy structures of the K_Ca2.2 channel in complex with calmodulin and Ca²⁺, alone or bound to two small molecule inhibitors, at 3.18, 3.50, 2.99 and 2.97 angstrom resolution, respectively. Extracellular S3-S4 loops in β-hairpin configuration form an outer canopy over the pore with an aromatic box at the canopy’s center. Each S3-S4 β-hairpin is tethered to the selectivity filter in the neighboring subunit by inter-subunit hydrogen bonds. This hydrogen bond network flips the aromatic residue (Tyr362) in the filter’s GYG signature by 180°, causing the outer selectivity filter to widen and water to enter the filter. Disruption of the tether by a mutation narrows the outer selectivity filter, realigns Tyr362 to the position seen in other K⁺ channels, and significantly increases unitary conductance. UCL1684, a mimetic of the bee venom peptide apamin, sits atop the canopy and occludes the opening in the aromatic box. AP14145, an analogue of a therapeutic for atrial fibrillation, binds in the central cavity below the selectivity filter and induces closure of the inner gate. These structures provide a basis for understanding the small unitary conductance and pharmacology of K_Ca2.x channels.

One group of the K⁺ ion channels, the small‐conductance Ca²⁺‐activated potassium channels (K_Ca2.x, also known as SK channels family), is widely expressed in neurons as well as the heart, endothelial cells, etc. They are named small‐conductance Ca²⁺‐activated potassium channels (SK channels) due to their comparatively low single‐channel conductance of about ~10 pS. These channels are insensitive to changes in membrane potential and are activated solely by rises in the intracellular Ca²⁺. According to the phylogenic research done on the K_Ca2.x channels family, there are three channels' subtypes: K_Ca2.1, K_Ca2.2, and K_Ca2.3, which are encoded by KCNN1, KCNN2, and KCNN3 genes, respectively. The K_Ca2.x channels regulate neuronal excitability and responsiveness to synaptic input patterns. K_Ca2.x channels inhibit excitatory postsynaptic potentials (EPSPs) in neuronal dendrites and contribute to the medium afterhyperpolarization (mAHP) that follows the action potential bursts. Multiple brain regions, including the hippocampus, express the K_Ca2.2 channel encoded by the KCNN2 gene on chromosome 5. Of particular interest, rat cerebellar Purkinje cells express K_Ca2.2 channels, which are crucial for various cellular processes during development and maturation. Patients with a loss‐of‐function of KCNN2 mutations typically exhibit extrapyramidal symptoms, cerebellar ataxia, motor and language developmental delays, and intellectual disabilities. Studies have revealed that autosomal dominant neurodevelopmental movement disorders resembling rodent symptoms are caused by heterozygous loss‐of‐function mutations, which are most likely to induce KCNN2 haploinsufficiency. The K_Ca2.2 channel is a promising drug target for spinocerebellar ataxias (SCAs). SCAs exhibit the dysregulation of firing in cerebellar Purkinje cells which is one of the first signs of pathology. Thus, selective K_Ca2.2 modulators are promising potential therapeutics for SCAs.

Redox regulation is crucial for the cardiac action potential, coordinating the sodium-driven depolarization, calcium-mediated plateau formation, and potassium-dependent repolarization processes required for proper heart function. Under physiological conditions, low-level reactive oxygen species (ROS), generated by mitochondria and membrane oxidases, adjust ion channel function and support excitation–contraction coupling. However, when ROS accumulate, they modify a variety of important channel proteins in cardiomyocytes, which commonly results in reducing potassium currents, enhancing sodium and calcium influx, and enhancing intracellular calcium release. These redox-driven alterations disrupt the cardiac rhythm, promote after-depolarizations, impair contractile force, and accelerate the development of heart diseases. Experimental models demonstrate that oxidizing agents reduce repolarizing currents, whereas reducing systems restore normal channel activity. Similarly, oxidative modifications of calcium-handling proteins amplify sarcoplasmic reticulum release and diastolic calcium leak. Understanding the precise redox-dependent modifications of cardiac ion channels would guide new possibilities for targeted therapies aimed at restoring electrophysiological homeostasis under oxidative stress, potentially alleviating myocardial infarction and cardiovascular dysfunction.

Parenteral nutrition (PN) is essential for patients who are unable to tolerate oral or enteral feeding, providing them with necessary nutrients intravenously, including dextrose, amino acids, electrolytes, vitamins, trace elements, and lipid emulsions. Clinical pharmacists (CPs) play a critical role in PN management by ensuring proper formulation, monitoring therapy, preventing complications, and optimizing patient outcomes. In Saudi Arabia, limited literature exists on CPs’ involvement in total parenteral nutrition (TPN) administration, health information management (HIM) systems, and pharmacist staffing ratios. This paper examines the evolving role of CPs in PN management, addressing key challenges such as the optimal patient-to-CP ratio, the impact of HIM systems on PN prescribing, and the advantages and limitations of centralized versus decentralized PN prescription models. It highlights the need for standardized staffing levels, structured pharmacist training, and improved HIM integration to enhance workflow efficiency and prescribing accuracy. Additionally, the study examines how the adoption of advanced HIM systems can streamline documentation, reduce prescribing errors, and enhance interdisciplinary collaboration. This paper provides a framework for optimizing PN delivery, enhancing healthcare quality, and strengthening CPs’ contributions to nutrition support by addressing these factors. Implementing these recommendations will improve patient outcomes and establish a more efficient PN management system in Saudi Arabia, reinforcing the vital role of CPs in multidisciplinary care.

K⁺ channels are involved in many critical functions in lung physiology. Recently, the family of Ca²⁺-activated K⁺ channels (K_Ca) has received more attention, and a massive amount of effort has been devoted to developing selective medications targeting these channels. Within the family of K_Ca channels, three small-conductance Ca²⁺-activated K⁺ (K_Ca2) channel subtypes, together with the intermediate-conductance K_Ca3.1 channel, are voltage-independent K⁺ channels, and they mediate Ca²⁺-induced membrane hyperpolarization. Many K_Ca2 channel members are involved in crucial roles in physiological and pathological systems throughout the body. In this article, different subtypes of K_Ca2 and K_Ca3.1 channels and their functions in respiratory diseases are discussed. Additionally, the pharmacology of the K_Ca2 and K_Ca3.1 channels and the link between these channels and respiratory ciliary regulations will be explained in more detail. In the future, specific modulators for small or intermediate Ca²⁺-activated K⁺ channels may offer a unique therapeutic opportunity to treat muco-obstructive lung diseases.