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Cold Spring Harbor Perspectives in... Aug 2011Voltage-gated calcium (Ca(2+)) channels are key transducers of membrane potential changes into intracellular Ca(2+) transients that initiate many physiological events.... (Review)
Review
Voltage-gated calcium (Ca(2+)) channels are key transducers of membrane potential changes into intracellular Ca(2+) transients that initiate many physiological events. There are ten members of the voltage-gated Ca(2+) channel family in mammals, and they serve distinct roles in cellular signal transduction. The Ca(V)1 subfamily initiates contraction, secretion, regulation of gene expression, integration of synaptic input in neurons, and synaptic transmission at ribbon synapses in specialized sensory cells. The Ca(V)2 subfamily is primarily responsible for initiation of synaptic transmission at fast synapses. The Ca(V)3 subfamily is important for repetitive firing of action potentials in rhythmically firing cells such as cardiac myocytes and thalamic neurons. This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties.
Topics: Animals; Calcium Channel Blockers; Calcium Channels; Calcium Signaling; Excitation Contraction Coupling; Humans; Models, Biological; Protein Structure, Quaternary; Protein Structure, Tertiary; Synaptic Transmission
PubMed: 21746798
DOI: 10.1101/cshperspect.a003947 -
Neuron May 2018Voltage-gated calcium channels couple depolarization of the cell-surface membrane to entry of calcium, which triggers secretion, contraction, neurotransmission, gene... (Review)
Review
Voltage-gated calcium channels couple depolarization of the cell-surface membrane to entry of calcium, which triggers secretion, contraction, neurotransmission, gene expression, and other physiological responses. They are encoded by ten genes, which generate three voltage-gated calcium channel subfamilies: Ca1; Ca2; and Ca3. At synapses, Ca2 channels form large signaling complexes in the presynaptic nerve terminal, which are responsible for the calcium entry that triggers neurotransmitter release and short-term presynaptic plasticity. Ca1 channels form signaling complexes in postsynaptic dendrites and dendritic spines, where their calcium entry induces long-term potentiation. These calcium channels are the targets of mutations and polymorphisms that alter their function and/or regulation and cause neuropsychiatric diseases, including migraine headache, cerebellar ataxia, autism, schizophrenia, bipolar disorder, and depression. This article reviews the molecular properties of calcium channels, considers their multiple roles in synaptic plasticity, and discusses their potential involvement in this wide range of neuropsychiatric diseases.
Topics: Animals; Calcium Channels; Calcium Signaling; Humans; Mental Disorders; Mutation; Neuronal Plasticity; Protein Structure, Secondary
PubMed: 29723500
DOI: 10.1016/j.neuron.2018.03.017 -
Pharmacological Reviews Oct 2015Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described... (Review)
Review
Voltage-gated calcium channels are required for many key functions in the body. In this review, the different subtypes of voltage-gated calcium channels are described and their physiologic roles and pharmacology are outlined. We describe the current uses of drugs interacting with the different calcium channel subtypes and subunits, as well as specific areas in which there is strong potential for future drug development. Current therapeutic agents include drugs targeting L-type Ca(V)1.2 calcium channels, particularly 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type (Ca(V)3) channels are a target of ethosuximide, widely used in absence epilepsy. The auxiliary subunit α2δ-1 is the therapeutic target of the gabapentinoid drugs, which are of value in certain epilepsies and chronic neuropathic pain. The limited use of intrathecal ziconotide, a peptide blocker of N-type (Ca(V)2.2) calcium channels, as a treatment of intractable pain, gives an indication that these channels represent excellent drug targets for various pain conditions. We describe how selectivity for different subtypes of calcium channels (e.g., Ca(V)1.2 and Ca(V)1.3 L-type channels) may be achieved in the future by exploiting differences between channel isoforms in terms of sequence and biophysical properties, variation in splicing in different target tissues, and differences in the properties of the target tissues themselves in terms of membrane potential or firing frequency. Thus, use-dependent blockers of the different isoforms could selectively block calcium channels in particular pathologies, such as nociceptive neurons in pain states or in epileptic brain circuits. Of important future potential are selective Ca(V)1.3 blockers for neuropsychiatric diseases, neuroprotection in Parkinson's disease, and resistant hypertension. In addition, selective or nonselective T-type channel blockers are considered potential therapeutic targets in epilepsy, pain, obesity, sleep, and anxiety. Use-dependent N-type calcium channel blockers are likely to be of therapeutic use in chronic pain conditions. Thus, more selective calcium channel blockers hold promise for therapeutic intervention.
Topics: Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Calcium Channels, N-Type; Calcium Channels, T-Type; Cardiovascular Diseases; Cyclic AMP-Dependent Protein Kinases; GTP-Binding Proteins; Hearing Disorders; Humans; Metabolic Diseases; Nervous System Diseases; Night Blindness; Phospholipids; Receptor Protein-Tyrosine Kinases
PubMed: 26362469
DOI: 10.1124/pr.114.009654 -
Neuron Apr 2014Voltage-gated calcium channels are the primary mediators of depolarization-induced calcium entry into neurons. There is great diversity of calcium channel subtypes due... (Review)
Review
Voltage-gated calcium channels are the primary mediators of depolarization-induced calcium entry into neurons. There is great diversity of calcium channel subtypes due to multiple genes that encode calcium channel α1 subunits, coassembly with a variety of ancillary calcium channel subunits, and alternative splicing. This allows these channels to fulfill highly specialized roles in specific neuronal subtypes and at particular subcellular loci. While calcium channels are of critical importance to brain function, their inappropriate expression or dysfunction gives rise to a variety of neurological disorders, including, pain, epilepsy, migraine, and ataxia. This Review discusses salient aspects of voltage-gated calcium channel function, physiology, and pathophysiology.
Topics: Animals; Brain Diseases; Calcium Channels; Humans; Neurons
PubMed: 24698266
DOI: 10.1016/j.neuron.2014.03.016 -
International Urology and Nephrology Nov 2022Accumulating evidences indicated that voltage-gated calcium channels (VDCC), including L-, T-, N-, and P/Q-type, are present in kidney and contribute to renal injury... (Review)
Review
Accumulating evidences indicated that voltage-gated calcium channels (VDCC), including L-, T-, N-, and P/Q-type, are present in kidney and contribute to renal injury during various chronic diseases trough different mechanisms. As a voltage-gated calcium channel, N-type calcium channel was firstly been founded predominately distributed on nerve endings which control neurotransmitter releases. Since sympathetic nerve is distributed along renal afferent and efferent arterioles, N-type calcium channel blockade on sympathetic nerve terminals would bring renal dynamic improvement by dilating both arterioles and reducing glomerular pressure. In addition, large body of scientific research indicated that neurotransmitters, such as norepinephrine, releases by activating N-type calcium channel can trigger inflammatory and fibrotic signaling pathways in kidney. Interestingly, we recently demonstrated that N-type calcium channel is also expressed on podocytes and may directly contribute to podocyte injury in denervated animal models. In this paper, we will summarize our current knowledge regarding renal N-type calcium channels, and discuss how they might contribute to the river that terminates in renal injury.
Topics: Animals; Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, N-Type; Kidney; Neurotransmitter Agents; Norepinephrine
PubMed: 35416563
DOI: 10.1007/s11255-022-03183-8 -
International Journal of Molecular... Mar 2021Migraine is a common neurological disease that affects about 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura and... (Review)
Review
Migraine is a common neurological disease that affects about 11% of the adult population. The disease is divided into two main clinical subtypes: migraine with aura and migraine without aura. According to the neurovascular theory of migraine, the activation of the trigeminovascular system (TGVS) and the release of numerous neuropeptides, including calcitonin gene-related peptide (CGRP) are involved in headache pathogenesis. TGVS can be activated by cortical spreading depression (CSD), a phenomenon responsible for the aura. The mechanism of CSD, stemming in part from aberrant interactions between neurons and glia have been studied in models of familial hemiplegic migraine (FHM), a rare monogenic form of migraine with aura. The present review focuses on those interactions, especially as seen in FHM type 1, a variant of the disease caused by a mutation in , which encodes the α1A subunit of the P/Q-type voltage-gated calcium channel.
Topics: Calcitonin Gene-Related Peptide; Calcium; Calcium Channels; Calcium Channels, N-Type; Humans; Migraine Disorders; Mutation; Neuroglia
PubMed: 33799975
DOI: 10.3390/ijms22052688 -
The Journal of General Physiology Jul 2013
Topics: Animals; Bacteria; Calcium Channels; Cockroaches; Endocytosis; Mechanotransduction, Cellular
PubMed: 23797418
DOI: 10.1085/jgp.201311041 -
Kidney International Mar 2000Calcium is an important intracellular signaling molecule, and altered calcium channel function can cause widespread cellular changes. Genetic mutations in calcium... (Review)
Review
Calcium is an important intracellular signaling molecule, and altered calcium channel function can cause widespread cellular changes. Genetic mutations in calcium channels that cause what appear to be trivial alterations of calcium currents in vitro can result in serious diseases in muscles and the nervous system. This article reviews calcium channelopathies in humans and mice.
Topics: Animals; Calcium Channels; Electrophysiology; Humans; Muscle, Skeletal; Muscular Diseases; Mutation; Nervous System Diseases; Structure-Activity Relationship
PubMed: 10720931
DOI: 10.1046/j.1523-1755.2000.00917.x -
British Journal of Pharmacology Jul 2013Degenerative dementia is mainly caused by Alzheimer's disease and/or cerebrovascular abnormalities. Disturbance of the intracellular calcium homeostasis is central to... (Review)
Review
Degenerative dementia is mainly caused by Alzheimer's disease and/or cerebrovascular abnormalities. Disturbance of the intracellular calcium homeostasis is central to the pathophysiology of neurodegeneration. In Alzheimer's disease, enhanced calcium load may be brought about by extracellular accumulation of amyloid-β. Recent studies suggest that soluble forms facilitate influx through calcium-conducting ion channels in the plasma membrane, leading to excitotoxic neurodegeneration. Calcium channel blockade attenuates amyloid-β-induced neuronal decline in vitro and is neuroprotective in animal models. Vascular dementia, on the other hand, is caused by cerebral hypoperfusion and may benefit from calcium channel blockade due to relaxation of the cerebral vasculature. Several calcium channel blockers have been tested in clinical trials of dementia and the outcome is heterogeneous. Nimodipine as well as nilvadipine prevent cognitive decline in some trials, whereas other calcium channel blockers failed. In trials with a positive outcome, BP reduction did not seem to play a role in preventing dementia, indicating a direct protecting effect on neurons. An optimization of calcium channel blockers for the treatment of dementia may involve an increase of selectivity for presynaptic calcium channels and an improvement of the affinity to the inactivated state. Novel low molecular weight compounds suitable for proof-of-concept studies are now available.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Calcium Signaling; Dementia; Disease Progression; Drugs, Investigational; Humans; Neurons; Nootropic Agents; Synaptic Transmission
PubMed: 23638877
DOI: 10.1111/bph.12240 -
The Journal of Physiology May 2017
Topics: Animals; Calcium Channels; Congresses as Topic; Humans; Physiology; Societies, Scientific
PubMed: 28503825
DOI: 10.1113/JP274289