The pacemaker current is a hyperpolarization-activated, cation-selective, inward current that modulates the firing rate of cardiac and neuronal pacemaker cells1. …
Continue readingIon Channels
The Inward Rectifier K+ Channel ROMK (Kir1.1)
The first of the distinctive family of two transmembrane domain inward rectifier K+ channels to be cloned was ROMK11, now …
By Alon Meir, Ph.D.
Continue reading Cyclic Nucleotide Gated (CNG) Channels
Cyclic nucleotide gated (CNG) channels are non-selective cation channels facilitating the influx of Na+ and Ca2+ ions, with their opening …
By Alon Meir, Ph.D.
Continue reading The KV4 Channel Subfamily (Shal)
The KV4 subfamily of voltage dependent K+ channels is the mammalian parallel of the Drosophila Shal K+ channel. These currents …
By Alon Meir, Ph.D.
Continue reading Ion Channels in Cancer
Ion channels have long been known to be involved in the regulation of a variety of biological functions ranging from the control of cell excitability to the regulation of cell volume and proliferation. Because of the ubiquitous presence of ion channels in virtually all cells and their critical involvement in diverse biological functions, it came as no surprise when several human and animal diseases were attributed to defects in ion channel function. Indeed, the term channelopathies was coined to describe the ever growing number of diseases associated with ion channel function. Channelopathies have been recognized in the context of conditions as diverse as epilepsy1, cardiac arrhythmias2, skeletal muscle disorders3 and diabetes4.
By Noemí Bronstein-Sitton, Ph.D.
Continue reading Large Conductance Ca2+-Dependent K+ (BKCa) Channels
Ca2+ dependent K+ (KCa) channels are divided according to biophysical properties and gene homology into two main groups. KCa were first divided according to their single channel conductance, which represents the speed by which the K+ passes via the open channel. The first group consists of small and intermediate conductance channels (SK and IK respectively, the KCNN gene family). The second group is comprised of large/big conductance channels (called BKCa or maxiK, encoded by the slo or KCNMA1 gene)1.
BKCa channels are both voltage and [Ca2+]in dependent and their response to both signals results in extensive K+ efflux (due to their large single channel conductance) and
By Alon Meir, Ph.D.
Continue reading Na+/H+ Exchanger Regulatory Factor-1 (NHERF-1): A PDZ-Domain Containing Protein Adaptor
The Na+/H+ exchanger regulatory factor (NHERF-1 or EBP-50) is a 55 kD cytoplasmic protein adaptor that recruits a wide variety of cellular proteins. Many of the interacting proteins do so through the two tandem PDZ domains (protein-binding domains conserved in the mammalian synaptic protein PSD-95/DlgA/ZO-1) and the C-terminal ERM (ezrin, radixin, moesin) binding region.
NHERF-1 was first identified as an adaptor necessary for the function of the Na+/H+ exchanger isoform 3(NHE3) in renal apical cells1. Since then it has been identified in cells of epithelial origin in several tissues such as gastrointestinal and lung. NHERF-1 has been shown to interact with a growing number of proteins including ion channels
By Noemí Bronstein-Sitton, Ph.D.
Continue reading Voltage-Dependent K+ (KV) Channels: A Large and Diverse Family of Membrane Voltage Regulators
K+ selective channels are some of the most widespread ion trafficking molecules in living organisms, with more than 70 genes encoding different K+ channels in humans.
K+ channels are gated by a variety of factors: voltage, cyclic nucleotides, ATP, Ca2+, Na+ and G-proteins, which may act singly or in combination. Therefore, many of these channels serve and operate as sensors for the cell’s metabolic state. In addition, K+ channels contribute to maintenance of a cell’s resting membrane potential and fine-tuning excitability in neurons, heart and muscle, mainly by defining the action potential duration and the intervals between them.
By Alon Meir, Ph.D.
Continue reading T-type CaV Channels
Voltage-dependent Ca2+ (CaV) channels form an important route for Ca2+ entry into cells, upon deviations from the cell’s resting membrane potential. Functionally, CaV channels are divided into Low Voltage-Activated (LVA) and High Voltage-Activated (HVA) channels1.
This functional division implies that cells respond differentially to small or large depolarization of the plasma membrane, activating two different classes of CaV channels, which conduct the Ca2+ inflow with different characteristics. T-type currents are carried out via channel proteins encoded by three genes that compose a subfamily within the CaV channels family (see Table 1)2-4. Several biophysical properties distinguish LVA from HVA CaV channels. The “T” stands for transient, resulting from the strong
By Alon Meir, Ph.D.
Continue reading Involvement of Ion Channels in Apoptosis
Involvement of ion channels in apoptosis is linked to critical aspects of this complex cellular process such as coordination of …
By Alon Meir, Ph.D.
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