KCNB1

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]
Diseases associated with KCNB1 include Developmental And Epileptic Encephalopathy 26 and Early Infantile Epileptic Encephalopathy. Among its related pathways are Integration of energy metabolism and Potassium Channels. Gene Ontology (GO) annotations related to this gene include monoatomic ion channel activity and voltage-gated potassium channel activity. An important paralog of this gene is KCNB2.
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system.
Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain (PubMed:23161216).
Plays also a role in the regulation of exocytosis independently of its electrical function (By similarity).
Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient.
The channel alternates between opened and closed conformations in response to the voltage difference across the membrane.
Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization (PubMed:10484328, 12560340, 1283219, 19074135, 19717558, 24901643, 8081723).
Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel (By similarity).
Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (PubMed:10484328, 11852086, 12060745, 19074135, 19717558, 24901643).
Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells (By similarity).
Channel properties are also modulated by cytoplasmic ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels (By similarity).
In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member.
Major contributor to the slowly inactivating delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle cells.
Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation.
Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus (By similarity).
Contributes to the regulation of glucose-induced action potential amplitude and duration in pancreatic beta cells, hence limiting calcium influx and insulin secretion (PubMed:23161216).
Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells.
May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval.
Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury.
May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions (By similarity).
Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits (PubMed:12060745).
Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner (By similarity).
Kinetic parameters: Note=Homotetrameric channels expressed in xenopus oocytes or in mammalian non-neuronal cells display delayed-rectifier voltage-dependent potassium currents which are activated during membrane depolarization, i.e within a risetime of about 20 msec (PubMed:1283219, 8081723).
After that, inactivate very slowly, i.e within more than 5 sec (PubMed:1283219, 8081723).
Their activation requires low threshold potentials of about -20 to -30 mV, with a midpoint activation at about 10 mV.
For inactivation, the voltage at half-maximal amplitude is about -20 mV (PubMed:11852086).
The time constant for recovery after inactivation is about 1.6 sec.
Channels have an unitary conductance of about 8 pS (PubMed:10484328).
The voltage-dependence of activation and inactivation and other channel characteristics vary depending on the experimental conditions, the expression system, the presence or absence of ancillary subunits and post-translational modifications.
{ECO:0000269 PubMed:10484328, 11852086, 1283219, 8081723 | ECO:0000305 PubMed:10414301, 15858231};
Inhibited by 12.7 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata (PubMed:14565763).
Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata (PubMed:14565763).
Modestly sensitive to millimolar levels of tetraethylammonium (TEA) (PubMed:1283219, 8081723).
Modestly sensitive to millimolar levels of 4-aminopyridine (4-AP).
Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX) (By similarity).
potassium voltage-gated channel,Drosophila Shab-related subfamily
Cell membrane {ECO:0000269 PubMed:10484328, 11852086, 12060745, 12560340, 1283219, 19074135, 19223394, 19717558, 24477962, 24901643, 26503721, 8081723}5
Perikaryon {ECO:0000269 PubMed:24477962}
Cell projection, axon {ECO:0000269 PubMed:24477962}
Cell projection, dendrite {ECO:0000269 PubMed:24477962}
Membrane; Multi-pass membrane protein
Postsynaptic cell membrane {ECO:0000250 UniProtKB:P15387}
Synapse {ECO:0000250 UniProtKB:P15387}
Synapse, synaptosome {ECO:0000250 UniProtKB:P15387}
Lateral cell membrane {ECO:0000250 UniProtKB:P15387}
Cell membrane, sarcolemma {ECO:0000250 UniProtKB:P15387}
Note: Localizes to high-density somatodendritic clusters and non-clustered sites on the surface of neocortical and hippocampal pyramidal neurons in a cortical actin cytoskeleton-dependent manner (PubMed:24477962). Localizes also to high-density clusters in the axon initial segment (AIS), at ankyrin-G-deficient sites, on the surface of neocortical and hippocampal pyramidal neurons (PubMed:24477962). KCNB1-containing AIS clusters localize either in close apposition to smooth endoplasmic reticulum cisternal organelles or with GABA-A receptor-containing synapses of hippocampal and cortical pyramidal neurons, respectively (PubMed:24477962). Localizes to high-density clusters on the cell surface of atrial and ventricular myocytes and at the lateral plasma membrane in epithelial cells. Localizes both to the axial and transverse tubules (T tubule) and sarcolemma in ventricular myocytes. Associated with lipid raft domains. In cortical neurons, apoptotic injuries induce de novo plasma membrane insertion in a SNARE-dependent manner causing an apoptotic potassium current surge {ECO:0000250 UniProtKB:P15387, Q03717 | ECO:0000269 PubMed:12060745, 19074135, 24477962, 24901643}
Quaternary structure:
Homotetramer or heterotetramer with KCNB2 (PubMed:1283219, 8081723).
Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1 (PubMed:10484328, 11852086, 12060745, 19074135, 19357235, 19717558, 24901643).
Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3 (By similarity).
Interacts with KCNV2 (PubMed:34535971).
Self-associates (via N-terminus and C-terminus) (PubMed:12560340, 24901643); self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel (By similarity).
Interacts (via C-terminus) with STX1A (via C-terminus); this decreases the rate of channel activation and increases the rate of channel inactivation in pancreatic beta cells, induces also neuronal apoptosis in response to oxidative injury as well as pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons.
Interacts (via N-terminus) with SNAP25; this decreases the rate of channel inactivation in pancreatic beta cells and also increases interaction during neuronal apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-dependent manner.
Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate.
Interacts with CREB1; this promotes channel acetylation in response to stimulation of incretin hormones.
Interacts (via N-terminus and C-terminus) with MYL12B.
Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface (By similarity).
Interacts with SUMO1 (PubMed:19223394).
Interacts (via phosphorylated form) with PTPRE; this reduces phosphorylation and channel activity in heterologous cells (By similarity).
Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (PubMed:33124732).