L-Type Calcium Channels are Modified in Rat Hippocampus by Short-Term Experimental Ischemia

Increasing evidence suggests a role for calcium ions in the pathophysiology of ischemic brain damage. The major mechanism allowing calcium entry from the extracellular compartment is the opening of voltage-operated calcium channels. In this line, we have explored the hypothesis that the characteristics of central L-type voltage-dependent calcium channels, labeled by the dihydropyridine ligand 3H-PN 200-110, may be modified by experimental ischemia. The results show that short-term mild ischemia, produced in the rat by 1 h of right carotid ligation, induces an increase in the number of 3H-PN 200-110 binding sites in the hippocampus ipsilateral to the side of carotid occlusion, accompanied by an increase in the dissociation constant value, whereas no changes in the kinetic parameters of the binding were observed in the other areas examined, i.e., the cortex and the striatum. The changes in hippocampus are transient: 96 h after the occlusion, binding parameters return to the control range. The modifications of the binding characteristics in the hippocampus may be related to alterations of Ca2+ fluxes through L-type calcium channels.

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Voltage-dependent calcium channels: structures and drug-binding sites

Biochemical Society Transactions ◽

10.1042/bst0200147 ◽

1992 ◽

Vol 20 (1) ◽

pp. 147-153 ◽

Cited By ~ 5

Author(s):

Michael Spedding ◽

Barry Kenny

Keyword(s):

Calcium Channels ◽

Binding Sites ◽

Drug Binding ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels ◽

Drug Binding Sites

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Opposing effects of noradrenaline on the two classes of voltage-dependent calcium channels of single vascular smooth muscle cells in short-term primary culture

Pflügers Archiv - European Journal of Physiology ◽

10.1007/bf00586539 ◽

1987 ◽

Vol 410 (4-5) ◽

pp. 557-559 ◽

Cited By ~ 46

Author(s):

P. Pacaud ◽

G. Loirand ◽

C. Mironneau ◽

J. Mironneau

Keyword(s):

Smooth Muscle ◽

Calcium Channels ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Primary Culture ◽

Vascular Smooth Muscle Cells ◽

Short Term ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels ◽

Opposing Effects

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Antagonist binding sites of voltage-dependent calcium channels

Drug Development Research ◽

10.1002/(sici)1098-2299(199711/12)42:3/4<131::aid-ddr4>3.0.co;2-r ◽

1997 ◽

Vol 42 (3-4) ◽

pp. 131-143 ◽

Cited By ~ 25

Author(s):

Gerald W. Zamponi

Keyword(s):

Calcium Channels ◽

Binding Sites ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels ◽

Antagonist Binding

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Alteration of Voltage-Dependent Calcium Channels in Canine Brain during Global Ischemia and Reperfusion

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1992.59 ◽

1992 ◽

Vol 12 (3) ◽

pp. 418-424 ◽

Cited By ~ 19

Author(s):

Paul J. Hoehner ◽

Thomas J. J. Blanck ◽

Rita Roy ◽

Robert E. Rosenthal ◽

Gary Fiskum

Keyword(s):

Ventricular Fibrillation ◽

Spontaneous Circulation ◽

Global Ischemia ◽

Affinity Constant ◽

Ischemia And Reperfusion ◽

Early Reperfusion ◽

Ischemic Brain ◽

Binding Characteristics ◽

Voltage Dependent ◽

Voltage Dependent Calcium Channels

Elevated intracellular calcium (iCa2+) plays an important role in the pathophysiology of ischemic brain damage. The mechanisms by which iCa2+ increases are uncertain. Recent evidence implicates the voltage-dependent calcium channel (VDCC) as a likely site for the alteration in Ca2+ homeostasis during ischemia. The purpose of this study was to determine whether VDCCs are altered by global ischemia and reperfusion in a canine cardiac arrest, resuscitation model. We employed the radioligand, [3H]PN200-110, to quantitate the equilibrium binding characteristics of the VDCCs in the cerebral cortex. Twenty-five adult beagles were separated into four experimental groups: (a) nonischemic controls, (b) those undergoing 10-min ventricular fibrillation and apnea, (c) those undergoing 10-min ventricular fibrillation and apnea followed by spontaneous circulation and controlled respiration for 2 and (d) 24 h. Brain cortex samples were taken prior to killing of the animal, frozen immediately in liquid nitrogen, and crude synaptosomal membranes isolated by differential centrifugation/filtration. After 10 min of ischemia the maximal binding (Bmax) of [3H]PN200-110 increased to >250% of control values (control Bmax 11.16 ± 0.98; ischemic 28.35 ± 2.78 fmol/mg protein; p < 0.05). Bmax returned to near control values after 2 h of reperfusion but remained significantly greater than the control at 24 h. Although the affinity constant (Kd) (control = 0.12 ± 0.03 n M) appeared to increase with ischemia and normalize with reperfusion, the changes were not statistically significant. We conclude that the binding of [3H]PN200-110 to L-type VDCCs is increased after 10 min of global ischemia/anoxia produced by ventricular fibrillation and apnea in the dog. This change is only partially reversible after 24 h of reperfusion. This study supports the hypothesis that ischemia increases the number of VDCCs in the cell membrane which may allow increased entry of Ca2+ into the cell during ischemia and early reperfusion.

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