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(Stroke. 2001;32:2624.)
© 2001 American Heart Association, Inc.

Original Contributions

Slowly Inactivating Potassium Conductance (I_D)

A Potential Target for Stroke Therapy

Jaideep S. Bains, PhD; Matthew J. Follwell, BSc; Kevin J. Latchford, BSc; James W. Anderson, PhD Alastair V. Ferguson, PhD

From the Department of Physiology, Queen’s University, Kingston, Ontario, Canada.

Correspondence to Alastair V. Ferguson, PhD, Department of Physiology, Queen’s University, Kingston, Ontario, Canada K7L 3N6. E-mail fergusna{at}post.queensu.ca

Background and Purpose—— Excessive accumulation of extracellular glutamate results in the death of most, but not all, neurons in the central nervous system. Understanding the unique properties of cells that can withstand this excitotoxic challenge may identify specific targets for novel stroke therapies.

Methods—— A combination of in vivo methods for analysis of excitotoxic cell death after activation of N-methyl-D-aspartate (NMDA) receptors and in vitro patch-clamp analysis of specific conductances in hypothalamic slices and dissociated cells has been used to assess the roles of specific potassium conductances in delayed cell death after NMDA receptor activation.

Results—— We report that a specific D-type potassium conductance (I_D), necessary for the rapid repolarization of the membrane after a strong depolarization, serves such a protective purpose in magnocellular neurons of the paraventricular nucleus. Manipulations that inhibit this current (4-aminopyridine or angiotensin II) increase neuronal excitability and augment cell death after NMDA receptor activation. In addition, this protection is not observed in magnocellular neurons of spontaneously hypertensive rats, and intriguingly it can be reestablished by blocking angiotensin II receptors in these animals.

Conclusions—— These observations provide a persuasive experimental explanation for the unexpected finding that therapeutic treatments for hypertension that block central as well as peripheral angiotensin type 1 receptors reduce the severity and occurrence of stroke.

Key Words: angiotensins • excitotoxicity • neuroprotection • N-methyl-D-aspartate • potassium channels • stroke, experimental • stroke prevention • rats

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