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PubMed1993

Development of NMDA receptor-channel complex and L-type calcium channels in mouse hippocampus.

In vitro binding autoradiography was used to examine the pattern and intensity of binding of [3H]glutamate to NMDA receptors, [3H]MK 801 to NMDA receptor associated channels, and [3H]PN-200 110 to L-type calcium channels in the hippocampus of mice aged 3-70 days. The distribution of NMDA receptors and NMDA receptor associated channels was similar but not identical at the tested ages. Beginning with postnatal day 8, high binding levels were confined mostly to the hippocampal strata: the oriens and radiatum (CA1 and CA3 with [3H]MK 801 labeling but only CA1 with NMDA displaced [3H]glutamate labeling), the moleculare (higher labeling with [3H]MK 801 than with NMDA displaced [3H]glutamate binding), and the lucidum. The binding values for NMDA receptor-channel complex rose in the examined period (especially within the second and third week), reaching a plateau at the end of the third postnatal week. Sharp growth of binding within the second and third week of life was about 50% greater with [3H]MK 801 than with NMDA displaced [3H] glutamate labeling. L-type calcium channels were found to be most abundant in the strata: the oriens of the CA3 field, the moleculare, and the lucidum. The time course of binding value changes for the calcium channel was similar to the time course found for the NMDA receptor-channel complex.

Age Factors↗

PubMed1984

Cellular actions and pharmacology of the calcium channel blocking drugs.

The calcium channel blockers represent a group of diverse chemical structures that block calcium-selective channels in the plasma membranes of a variety of excitable cells. As the calcium fluxes carried by these channels allow the calcium ion (Ca2+) to gain access to the cell interior, where calcium serves as an activator messenger, calcium channel blockers generally act to inhibit cell function. By reducing the depolarizing currents caused by the entry of positively charged Ca2+ into the negatively charged interior of resting cells, the calcium channel blockers also inhibit excitatory processes that depend on calcium entry across the plasma membrane. These principles account for most of the effects of calcium channel blockers on the cardiovascular system. The calcium channel blockers inhibit contractile function in the heart and vascular smooth muscle and, because the initial depolarizing currents in the sinoatrial and atrioventricular nodes are carried by calcium channels, slow the heart rate and prolong atrioventricular conduction. The negative inotropic and vasodilatory effects of the calcium channel blockers, both of which can reduce systemic blood pressure, offer a theoretic basis for their potential use in the treatment of hypertension. The tissue specificity exhibited by some of the calcium channel blockers may enhance their therapeutic value in selected hypertensive patients. Of the three calcium channel blockers now available for use in the United States (diltiazem, nifedipine, and verapamil), diltiazem and verapamil are approximately equipotent in inhibiting calcium channel function in the heart and vascular smooth muscle, whereas nifedipine is more potent in smooth muscle. This tissue specificity can be used to advantage in the management of hypertension. These pharmacologic principles underlie the growing appreciation of the potential value of the calcium channel blockers in the treatment of hypertension.

Action Potentials↗

PubMed1985

Cellular actions and pharmacology of calcium-channel blockers.

The calcium-channel blockers represent a diverse group of chemical structures that block calcium-selective channels in the plasma membrane of a variety of excitable cells. As the calcium fluxes carried by these channels allow ionic calcium (Ca2+) to gain access to the cell interior, where Ca2+ serves as an activator--messenger, calcium-channel blockers generally act to inhibit cell function. By reducing the depolarizing currents caused by the entry of positively charged Ca2+ into the negatively charged interior of resting cells, the calcium-channel blockers also inhibit excitatory processes that depend on calcium entry across the plasma membrane. These principles account for most of the effects of calcium-channel blockers on the cardiovascular system. In vivo, the calcium-channel blockers inhibit contractile function in the heart and vascular smooth muscle and, because the initial depolarizing currents in the sinoatrial and atrioventricular nodes are carried by calcium channels, slow the heart rate and prolong atrioventricular conduction. However, in vivo in human studies, there are differences among the calcium-channel blockers. The vasodilatory effects of the calcium channel blockers, which can reduce systemic blood pressure, offer a primary basis for their potential use in the treatment of hypertension. The tissue specificity exhibited by some of the calcium-channel blockers may enhance their therapeutic value in selected hypertensive patients. Of the three calcium-channel blockers now available for use in the United States (diltiazem, nifedipine, and verapamil), diltiazem and verapamil are approximately equipotent in inhibiting calcium-channel function in cardiac and vascular smooth muscle, whereas nifedipine is more potent in vascular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗

PubMed1999

Regulation of type 1 inositol 1,4,5-trisphosphate-gated calcium channels by InsP3 and calcium: Simulation of single channel kinetics based on ligand binding and electrophysiological analysis.

Cytosolic calcium acts as both a coagonist and an inhibitor of the type 1 inositol 1,4,5-trisphosphate (InsP3)-gated Ca channel, resulting in a bell-shaped Ca dependence of channel activity (Bezprozvanny, I., J. Watras, and B.E. Ehrlich. 1991. Nature. 351:751-754; Finch, E.A., T.J. Turner, and S.M. Goldin. 1991. Science. 252: 443-446; Iino, M. 1990. J. Gen. Physiol. 95:1103-1122). The ability of Ca to inhibit channel activity, however, varies dramatically depending on InsP3 concentration (Combettes, L., Z. Hannaert-Merah, J.F. Coquil, C. Rousseau, M. Claret, S. Swillens, and P. Champeil. 1994. J. Biol. Chem. 269:17561-17571; Kaftan, E.J., B.E. Ehrlich, and J. Watras. 1997. J. Gen. Physiol. 110:529-538). In the present report, we have extended the characterization of the effect of cytosolic Ca on both InsP3 binding and InsP3-gated channel kinetics, and incorporated these data into a mathematical model capable of simulating channel kinetics. We found that cytosolic Ca increased the Kd of InsP3 binding approximately 3.5-fold, but did not influence the maximal number of binding sites. The ability of Ca to decrease InsP3 binding is consistent with the rightward shift in the bell-shaped Ca dependence of InsP3-gated Ca channel activity. High InsP3 concentrations are able to overcome the Ca-dependent inhibition of channel activity, apparently due to a low affinity InsP3 binding site (Kaftan, E.J., B.E. Ehrlich, and J. Watras. 1997. J. Gen. Physiol. 110:529-538). Constants from binding analyses and channel activity determinations were used to develop a mathematical model that fits the complex Ca-dependent regulation of the type 1 InsP3-gated Ca channel. This model accurately simulated both steady state data (channel open probability and InsP3 binding) and kinetic data (channel activity and open time distributions), and yielded testable predictions with regard to the regulation of this intracellular Ca channel. Information gained from these analyses, and our current molecular model of this Ca channel, will be important for understanding the basis and regulation of intracellular Ca waves and oscillations in intact cells.

Animals↗

PubMed1995

Calcium channel activation mobilizes calcium from a restricted pericellular region surrounding canine coronary artery smooth muscle cells.

Functional responses and subcellular calcium redistribution were compared in extramural canine coronary arteries to determine the ultrastructural source of calcium for depolarization-induced contractions. The subcellular distribution of total (bound and free) 45Ca in coronary artery smooth muscle was determined using 45Ca electron microscopic autoradiography procedures described previously (Wheeler-Clark et al., 1986). Relative 45Ca activities were compared for ultrastructural regions that included the plasma membrane (PM) region and sarcoplasmic reticulum in canine coronary smooth muscle frozen in control and high K+ solutions in the presence and absence of 3 x 10(-7) M nitrendipine. The 45Ca activity of SR was similar in contracted and relaxed muscle cells; thus, sarcoplasmic reticulum Ca2+ release was not observed as a result of K(+)-induced contraction in canine coronary arteries. However, the 45Ca activity of the PM was reduced by 75% in K(+)-contracted cells (P < .05). Inasmuch as nitrendipine completely inhibited both contraction and 45Ca loss from the PM region of high K(+)-depolarized cells, we suggest that the decreased relative 45Ca activity in the PM region of K(+)-contracted cells is due to Ca2+ redistribution from the pericellular space into the cytosol during Ca2+ channel activation. Data obtained using electron probe x-ray microanalysis also indicate that extracellular Ca2+ loss was restricted to the pericellular space within 100 nm of the membrane bilayer. As a model to explain our data, we suggest that: 1) calcium bound to the glycocalyx buffers the free Ca2+ that enters the cell through activated, Ca2+ channels and 2) a diffusion barrier at the outer edge of the glycocalyx promotes and prolongs this calcium buffering.

Animals↗

PubMed1996

Modulation of nicotine-evoked [3H]dopamine release from rat striatal synaptosomes by voltage-sensitive calcium channel ligands.

The calcium channel subtypes mediating nicotine-evoked [3H]dopamine release from rat striatal synaptosomes were probed with L-, N-, and P-type calcium channel ligands. Responses to nicotine were blocked by the peptides omega-conotoxin GVIA and omega-agatoxin IVA. The affinity constants for these compounds were consistent with their actions at N- and P-type channels, respectively. Together, these channels mediate at least 90% of the calcium-dependent response to nicotine. The L-type antagonists nifedipine, verapamil, and nicardipine were also effective blockers of nicotine-evoked release with maximal effects of 80-100% inhibition. However, these effects occurred at concentrations 2-3 orders of magnitude higher than those necessary to block L-type channels. Moreover, Bay K8644, an L-type agonist, also blocked nicotine-evoked release. Together, these findings argue strongly against the involvement of L-type channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed2004

Blockade of L-type calcium channel in myocardium and calcium-induced contractions of vascular smooth muscle by CPU 86017.

AIM: To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca(2+)-related contractions of vascular smooth muscle. METHODS: The whole-cell patch-clamp was applied to investigate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contractions by KCl or phenylephrine (Phe) of the isolated rat tail arteries were measured. RESULTS: Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent manner and with no influence on the activation and inactivation curves. The IC(50) was 11.5 micromol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KCl 100 mmol/L, phenylephrine 1 micromol/L in KH solution (phase 1), Ca(2+) free KH solution ( phase 2), and by addition of CaCl(2) into Ca(2+)-free KH solution (phase 3) were observed. The IC(50) to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and voltage-dependent channel (VDC) was 0.324 micromol/L and 16.3 micromol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca(2+) entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively. CONCLUSION: The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.

Animals↗

PubMed1992

Structure and functional expression of an omega-conotoxin-sensitive human N-type calcium channel.

N-type calcium channels are omega-conotoxin (omega-CgTx)-sensitive, voltage-dependent ion channels involved in the control of neurotransmitter release from neurons. Multiple subtypes of voltage-dependent calcium channel complexes exist, and it is the alpha 1 subunit of the complex that forms the pore through which calcium enters the cell. The primary structures of human neuronal calcium channel alpha 1B subunits were deduced by the characterization of overlapping complementary DNAs. Two forms (alpha 1B-1 and alpha 1B-2) were identified in human neuroblastoma (IMR32) cells and in the central nervous system, but not in skeletal muscle or aorta tissues. The alpha 1B-1 subunit directs the recombinant expression of N-type calcium channel activity when it is transiently co-expressed with human neuronal beta 2 and alpha 2b subunits in mammalian HEK293 cells. The recombinant channel was irreversibly blocked by omega-CgTx but was insensitive to dihydropyridines. The alpha 1B-1 alpha 2b beta 2-transfected cells displayed a single class of saturable, high-affinity (dissociation constant = 55 pM) omega-CgTx binding sites. Co-expression of the beta 2 subunit was necessary for N-type channel activity, whereas the alpha 2b subunit appeared to modulate the expression of the channel. The heterogeneity of alpha 1B subunits, along with the heterogeneity of alpha 2 and beta subunits, is consistent with multiple, biophysically distinct N-type calcium channels.

Amino Acid Sequence↗

PubMed1998

Overview of voltage-dependent calcium channels.

Voltage-dependent calcium channels couple electrical signals to cellular responses in excitable cells. Calcium channels are crucial for excitation-secretion coupling in neurons and endocrine cells, and excitation-contraction coupling in muscle. Several pharmacologically and kinetically distinct calcium channel types have been identified at the electrophysiological and molecular levels. This review summarizes the basic properties of voltage-dependent calcium channels, including mechanisms of ion permeation and block, gating kinetics, and modulation by G proteins and second messengers.

Animals↗

PubMed2005

Voltage-dependent calcium channels.

Voltage-activated calcium channels can be divided into two subgroups based on their activation threshold, low-voltage-activated (LVA) and high-voltage-activated (HVA). Auxiliary subunits of the HVA calcium channels contribute significantly to biophysical properties of the channels. We have cloned and characterized members of two families of auxiliary subunits: alpha2delta and gamma. Two new alpha2delta subunits, alpha2delta-2 and alpha2delta-3, regulate all classes of HVA calcium channels. While the ubiquitous alpha2delta-2 modulates both neuronal and non-neuronal channels with similar efficiency, the alpha2delta-3 subunit regulates Ca(v)2.3 channels more effectively. Furthermore, alpha2delta-2 may modulate the LVA Ca(v)3.1 channel. Four new gamma subunits, gamma-2, gamma-3, gamma-4 and gamma-5, were characterized. The gamma-2 subunit modulated both the non-neuronal Ca(v)1.2 channel and the neuronal Ca(v)2.1 channel. The gamma-4 subunit affected only the Ca(v)2.1 channel. The gamma-5 subunit may be a regulatory subunit of the LVA Ca(v)3.1 channel. The Ca(v)1.2 channel is a major target for treatment of cardiovascular diseases. We have mapped the interaction site for clinically important channel blockers - dihydropyridines (DHPs) - and analysed the underlying inhibition mechanism. High-affinity inhibition is characterized by interaction with inactivated state of the channel. Its structural determinants are amino acids of the IVS6 segment, with smaller contribution of the IS6 segment, which contributes to voltage-dependence of DHP inhibition. Removal of amino acids responsible for the high-affinity inhibition revealed a low-affinity open channel block, in which amino acids of the IIIS5 and IIIS6 segments take part. Experiments with a permanently charged DHP suggested that there is another low-affinity interaction site on the alpha(1) subunit. We have cloned and characterized murine neuronal LVA Ca(v)3.1 channel. The channel has high sensitivity to the organic blocker mibefradil, moderate sensitivity to phenytoin, and low sensitivity to ethosuximide, amiloride and valproat. The channel is insensitive to tetrodotoxin and DHPs. The inorganic blockers Ni2+ and Cd2+ are moderately effective compared to La3+. The current through the Ca(v)3.1 channel inactivates faster with Ba2+ compared to Ca2+. Molecular determinants of fast inactivation are located in amino side of the intracellular carboxy terminus. The voltage dependence of charge movement is very shallow compared to the voltage dependence of current activation. Transfer of 30 % of charge correlates with activation of 70 % of measurable macroscopic current. Prolonged depolarization does not immobilize charge movement of the Ca(v)3.1 channel.

Animals↗

PubMed1993

Calcium channel function in hypertension.

Calcium channel function is fundamental to membrane excitation in vascular muscle, and imparts the notable voltage sensitivity to small blood vessels. The actions of the electrogenic sodium pump on membrane potential, and thus calcium channels, can explain perturbations that could alternately be conceived as acting on other mechanisms. Evidence for altered calcium channel function in hypertension suggests that deficiencies in function of the calcium channel per se lie at the root of altered membrane function. In this respect the disease may be similar to at least one form of skeletal muscle dysgenesis. Proportional increases in BP and Ca2+ current in vascular muscle of stroke-prone genetically hypertensive rats further strengthen this hypothesis of altered Ca2+ channel function in hypertension. Increased calcium in the subsarcolemmal space and several recently discovered substances that may endogenously modulate Ca2+ channels are additional evidence for abnormal Ca2+ channel function in BP regulation. From several kinds of evidence and multiple investigators, it is reasonable to conclude that calcium channel malfunction plays an important role in the vascular muscle contribution to hypertension.

Animals↗

PubMed2004

Smooth muscle-selective alternatively spliced exon generates functional variation in Cav1.2 calcium channels.

Voltage-gated calcium channels play a major role in many important processes including muscle contraction, neurotransmission, excitation-transcription coupling, and hormone secretion. To date, 10 calcium channel alpha(1)-subunits have been reported, of which four code for L-type calcium channels. In our previous work, we uncovered by transcript-scanning the presence of 19 alternatively spliced exons in the L-type Ca(v)1.2 alpha(1)-subunit. Here, we report the smooth muscle-selective expression of alternatively spliced exon 9(*) in Ca(v)1.2 channels found on arterial smooth muscle. Specific polyclonal antibody against exon 9(*) localized the intense expression of 9(*)-containing Ca(v)1.2 channels on the smooth muscle wall of arteries, but the expression on cardiac muscle was low. Whole-cell patch clamp recordings of the 9(*)-containing Ca(v)1.2 channels in HEK293 cells demonstrated -9 and -11-mV hyperpolarized shift in voltage-dependent activation and current-voltage relationships, respectively. The steady-state inactivation property and sensitivity to blockade by nifedipine of the +/-exon 9(*) splice variants were, however, not significantly different. Such cell-selective expression of an alternatively spliced exon strongly indicates the customization and fine tuning of calcium channel functions through alternative splicing of the pore-forming alpha(1)-subunit. The generation of proteomic variations by alternative splicing of the calcium channel Ca(v)1.2 alpha(1)-subunit can potentially provide a flexible mechanism for muscle or neuronal cells to respond to various physiological signals or to diseases.

Alternative Splicing↗

PubMed1986

Occult Drosophila calcium channels and twinning of calcium and voltage-activated potassium channels.

In the membrane of the flight muscle cells of developing Drosophila a large calcium-sensitive potassium current, IKc, was found. It was present before the development of voltage-activated potassium channels and seems to be the first potassium current to develop in the membrane. Also present in these early cells were large numbers of occult (hidden) calcium channels, which remained inactive until the end of pupal development. These inactive calcium channels could be made to function by injecting adenosine triphosphate or ethyleneglycol tetraacetic acid into the early cells. IKc has kinetic properties resembling the later developing voltage-sensitive current IKv, and is distinct from the fast, transient calcium-dependent outward current IAc, which appears much later in development. IAc closely resembles the voltage-sensitive current IAv, also present in these cells. Thus, both of the voltage-sensitive potassium channel types, IAv and IKv, have similar calcium-sensitive counterparts, IAc and IKc, that are present in the same cells.

Action Potentials↗

PubMed2005

A unified model of presynaptic release site gating by calcium channel domains.

Calcium ions enter through discrete ion channels at presynaptic nerve terminals before binding to and activating transmitter release sites. Opposing models hold that release sites are gated either by calcium domains of single, closely associated channels or by extensive, overlapping domains from many remote channels. At the chick calyx synapse we find a linear relation between transmitter release and the number of open calcium channels, favouring single domain activation. This finding is consistent with results from the squid giant synapse but contrasts with steep power dependences reported in rodent synapses, suggestive of activation by extensive overlapping domains. These different reports were reconciled by plotting 'per cent domain overlap' against the external calcium concentration used for each species. This relationship predicts the involvement of local channels in the activation of release sites in all species. Further, it suggests that each release site is activated by calcium ions from its immediately associated channels and not by ions that enter through channels associated with a neighbouring release site.

Animals↗

PubMed1998

Structures and functions of calcium channel beta subunits.

Calcium channel beta subunits have profound effects on how alpha1 subunits perform. In this article we summarize our present knowledge of the primary structures of beta subunits as deduced from cDNAs and illustrate their different properties. Upon co-expression with alpha1 subunits, the effects of beta subunits vary somewhat between L-type and non-L-type channels mostly because the two types of channels have different responses to voltage which are affected by beta subunits, such as long-lasting prepulse facilitation of alpha1C (absent in alpha1E) and inhibition by G protein betagamma dimer of alpha1E, absent in alpha1C. One beta subunit, a brain beta2a splice variant that is palmitoylated, has several effects not seen with any of the others, and these are due to palmitoylation. We also illustrate the finding that functional expression of alpha1 in oocytes requires a beta subunit even if the final channel shows no evidence for its presence. We propose two structural models for Ca2+ channels to account for "alpha1 alone" channels seen in cells with limited beta subunit expression. In one model, beta dissociates from the mature alpha1 after proper folding and membrane insertion. Regulated channels seen upon co-expression of high levels of beta would then have subunit composition alpha1beta. In the other model, the "chaperoning" beta remains associated with the mature channel and "alpha1 alone" channels would in fact be alpha1beta channels. Upon co-expression of high levels of beta the regulated channels would have composition [alpha1beta]beta.

Amino Acid Sequence↗

PubMed1987

Brain extraction of a calcium channel blocker.

Dihydropyridine calcium channel blockers may be effective treatment for acute cerebral ischemia, but the uptake of these drugs into the brain is unknown. A 0.2-ml bolus of [14C]nicardipine hydrochloride and [3H]water was injected into the common carotid arteries of 7 normal and 7 ischemic rats. The corrected first-pass extraction of nicardipine, compared to water, was calculated to be 30.7% into the hemispheres and 42.3% into the hippocampi. The uptake was greater into the ischemic hemispheres (p less than 0.001). These data suggest that dihydropyridines are available to binding sites and calcium channels in neurons.

Animals↗

PubMed1988

Spatial distribution of calcium channels and cytosolic calcium transients in growth cones and cell bodies of sympathetic neurons.

Ca2+ imaging and single-channel recording were used to study the regulation of cytosolic free Ca2+ ([Ca2+]i) in local regions of frog sympathetic neurons. Digital imaging with the fluorescent Ca2+ indicator fura-2 demonstrated: (i) resting [Ca2+]i of 70-100 nM; (ii) significant increases in [Ca2+]i in growth cones and cell bodies following depolarization induced by extracellular electrical stimulation or increased external K+; (iii) in cell bodies, large transient increases in [Ca2+]i following exposure to caffeine and sustained oscillations in [Ca2+]i in the presence of elevated K+ and caffeine; and (iv) in growth cones, smaller and briefer changes in [Ca2+]i in response to caffeine. The nature of the depolarization-induced Ca2+ entry was studied with cell-attached patch recordings (110 mM Ba2+ in recording pipette). Ca2+ channel activity was observed in 18 of 20 patches on cell bodies, 3 of 5 patches along neurites, and 36 of 41 patch recordings from growth cones. We observed two types of Ca2+ channels: L-type channels, characterized by a 28-pS slope conductance, sensitivity to dihydropyridine Ca2+ channel agonist, and availability even with depolarizing holding potentials; and N-type channels, characterized by a 15-pS slope conductance, resistance to dihydropyridines, and inactivation with depolarized holding potentials. Both types of channels were found on growth cones and along neurites as well as on cell bodies; channels often appeared concentrated in local hot spots, sometimes dominated by one channel type.

Action Potentials↗

PubMed1999

Effects of an N-type calcium channel antagonist (SNX 111; Ziconotide) on calcium-45 accumulation following fluid-percussion injury.

Accumulation of calcium following experimental traumatic brain injury (TBI) has been demonstrated to be a prominent pathophysiological component that can compromise mitochondrial functioning and threaten cell survival. The omega-conopeptide SNX-111, also known as Ziconotide, is a potent antagonist of the voltage-gated N-type calcium channel and has demonstrated significant neuroprotective effects against ischemia-induced neuronal injury. To determine whether this compound would be effective in reducing calcium accumulation associated with TBI, SNX-111 was administered intravenously to rats 1 hour following a moderate (2.2 to 2.75 atm) lateral fluid-percussion injury (or sham) at doses of 1 (n = 30), 3 (n = 31), or 5 (n = 30) mg/kg; another group received 0.9% saline solution (n = 35). Brains were processed for calcium 45 (45Ca) autoradiography at 6, 12, 24, 48, and 96 hours following insult. Optical density measurements of 20 cortical and subcortical regions were analyzed. Injured animals administered saline solution exhibited a significant increase in 45Ca uptake within 12 regions ipsilateral to the site of injury. The most prominent increases were evident throughout the ipsilateral cerebral cortex. SNX-111 reduced the injury-induced calcium accumulation within the ipsilateral cortex in a dose-response fashion when measured at 6, 12, and 48 hours after insult. These drug-induced reductions in calcium accumulation were as high as 75% in the ipsilateral cerebral cortex, and up to 50% in other ipsilateral regions (including thalamus and hippocampus). Consequently, the results suggest that posttraumatic blocking of the voltage-gated N-type calcium channel after injury reduces prolonged, trauma-induced calcium accumulation.

Animals↗