Brief reviewsCa2+ Channel α1B Subunit (CaV 2.2) Knockout Mouse Reveals a Predominant Role of N-Type Channels in the Sympathetic Regulation of the Circulatory System
Section snippets
Selective and Complete Elimination of N-Type Channels by Disruption of α1B Subunit Gene
The Ca2+ channel classification, including “N type,” was initiated by Tsien and colleagues (Nowycky et al. 1985). “N type” was originally used to designate only the decaying component, whereas all the sustained components were grouped together as one L-type channel (Nowycky et al. 1985). Because the toxin suppressed both the decaying and sustained currents, both the N-type channel resistant to L-type channel blockers such as DHP and the L-type channel were reported to be susceptible to
Impaired Inotropic Contraction in Isolated Atria from N-Type-Deficient Mice
Sympathetic neurons have been considered to be a useful system in which to relate VDCC activity quantitatively with the downstream cellular response, that is, neurotransmitter release (Hirning et al. 1988). It is also well established that sympathetic nerves and parasympathetic nerves modulate the contractile force of atria in opposite directions: norepinephrine released from sympathetic nerve endings potentiates VDCC current through the β-adrenergic receptor stimulation to increase the atrial
Chronic Elevation of Blood Pressure and Heart Rate, and Impaired Baroreflex in N-Type Channel-Deficient Mice
N-type channel-deficient mice were expected to show hypotension, because previous reports demonstrated hypotension by administration of ω-CgTx-GVIA in animal models Bond and Boot 1992, Pruneau and Angus 1990. However, the genetic deficit of N-type VDCCs clearly led to higher levels of mAP and heart rate (HR) in our measurement of arterial blood pressure (AP) and HR in the carotid artery. Mean AP (mAP) and HR in knockout mice were 102.0 ± 4.3 mm Hg and 714.0 ± 11.5 beats per min (mean ± SE),
N-Type Knockout Mice as a Model for Autonomic Nervous Diseases
It is known that many patients suffering from primary autonomic failure show supine hypertension in addition to orthostatic hypotension Shannon et al. 1997, Vagaonescu et al. 2000. Because the mechanism of supine hypertension has not yet been fully clarified, it should be interesting to examine whether attenuation of sympathetic activity by downregulation of N-type VDCCs can be a cause of primary autonomic failure, because the N-type VDCC null mice showed hypertension and lack of baroreflex
References (54)
- et al.
The effect of calcium channel modulators on blood pressure and pressor responses to noradrenaline in the guinea-pig
Eur J Pharmacol
(1992) - et al.
Calcium channel gamma subunits provide insights into the evolution of this gene family
Gene
(2001) - et al.
Molecular cloning of a murine N-type calcium channel α-1 subunitevidence for isoforms, brain distribution, and chromosomal localization
FEBS Lett
(1994) - et al.
Nomenclature of voltage-gated calcium channels
Neuron
(2000) - et al.
ϕ conus geographus toxina peptide that blocks calcium channels
FEBS Lett
(1987) - et al.
Primary structure and functional expression of the ω-conotoxin-sensitive N-type calcium channel from rabbit brain
Neuron
(1993) - et al.
Altered nociceptive response in mice deficient in the α1B subunit of the voltage-dependent calcium channel
Mol Cell Neurosci
(2001) - et al.
Ca2+ channel antagonists and neuroprotection from cerebral ischemia
Eur J Physiol
(1998) - et al.
The association of endogenous Go alpha with the purified ω-conotoxin GVIA receptor
J Biol Chem
(1994) - et al.
Molecular pharmacology of voltage-dependent calcium channels
Jpn J Pharmacol
(1996)
Elementary properties and pharmacological sensitivities of calcium channels in mammalian peripheral neurons
Neuron
Ca2+ channels in rat central and peripheral neuronshigh-threshold current resistant to dihydropyridine blockers and ω-conotoxin
Neuron
Calcium ions, active zones and synaptic transmitter release
Trends Neurosci
Distribution of the ω-conotoxin receptor in rat brainan autoradiographic mapping
Neuroscience
Localization of mRNAs of voltage-dependent Ca2+ channelsfour subtypes of α1- and β-subunits in developing and mature rat brain
Mol Brain Res
Hypertensive cardiovascular damage in patients with primary autonomic failure
Lancet
Effects of ω-conotoxins on noradrenergic neurotransmission in beating guinea pig atria
Eur J Pharmacol
Subunit interaction sites in voltage-dependent Ca2+ channelsrole in channel function
Trends Neurosci
Relationship between autonomic function and progression of renal disease in diabetic proteinuriaclinical correlations and implications for blood pressure control
Am J Hypertens
Biochemical properties and subcellular distribution of an N-type calcium channel α1 subunit
Neuron
Distribution of N-type Ca2+ channel binding sites in rabbit brain following central administration of ω-conotoxin GVIA
Eur J Pharmacol
Structure and functional expression of α1, α2, and β subunits of a novel human neuronal calcium channel subtype
Neuron
Effects of ω-conotoxin GVIA on cardiac sympathetic nerve function
J Auton Nerv Syst
ω-conotoxin GVIA and desipramine insensitive norepinephrine efflux from cardiac sympathetic nerve terminal
Brain Res
Characterization of two kinds of high-voltage-activated Ca-channel currents in chick sensory neuronsdifferential sensitivity to dihydropyridines and ω-conotoxin GVIA
Pflügers Arch
Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure
N Engl J Med
Molecular cloning of the α-1 subunit of an ω-conotoxin-sensitive calcium channel
Proc Natl Acad Sci USA
Cited by (35)
The organ-protective effect of N-type Ca<sup>2+</sup> channel blockade
2015, Pharmacology and TherapeuticsVoltage-dependent N-type Ca<sup>2+</sup> channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice
2013, Biochemical and Biophysical Research CommunicationsCitation Excerpt :Cilnidipine was synthesized in Ajinomoto Pharmaceutical Co. Ltd. The Cav 2.2-deficient mice were developed by Dr. Yasuo Mori [14,22]. Their wild-type littermates (WT) served as the controls for all the studies.
Presynaptic stimulus-release and postsynaptic compensatory changes in mice lacking the N-type calcium channel α <inf>1B</inf>-subunit
2011, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :Contraction mediated by α-ADR receptors or thromboxane A2 receptors was potentiated in isolated thoracic aortas from N-type−/− mice. Mechanisms of chronic hypertension in N-type KO mice were hypothetically attributed to increased numbers of the α-ADR receptors, an increased supply of Ca2+ and enhanced expression of contractile proteins (Mori et al., 2002). We have found that changes in Gq-mediated cardiac responses in the hearts of the N-type−/− mice are similar to those reported in the vascular bed and attributed this increased responsiveness to target protein PLCβ1.
Supraspinal contribution to splanchnic sympathetic activity in neonatal mouse and rat brainstem-spinal cord in vitro
2010, Autonomic Neuroscience: Basic and ClinicalHistological protection by cilnidipine, a dual L/N-type Ca<sup>2+</sup> channel blocker, against neurotoxicity induced by ischemia-reperfusion in rat retina
2009, Experimental Eye ResearchCitation Excerpt :VDCCs have been divided into at least 5 types, comprised of L-, N-, T-, P- and Q-type, based on electrophysiological and biological evidences (Mori et al., 1996). N-type Ca2+ channels have been considered to regulate the systemic cardiovascular tone, because the channels are abundantly expressed on the sympathetic nerve endings, and predominantly regulate releases of catecholamine (Hirning et al., 1988; Mori et al., 2002). In addition, N-type Ca2+ channels are principally responsible for release of synaptic glutamate in the most of the central nervous system (Reid et al., 2003).