BAPTA-AM and ethanol protect cerebellar granule neurons from the destructive effect of the weaver gene

• Published in: Journal of neuroscience research Vol. 48; no. 6; pp. 571 - 579
• Main Authors: Liesi, Päivi, Wright, Jerry M., Krauthamer, Victor
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 15-06-1997
• Subjects: Animals; BAPTA-AM; Biological Transport - drug effects; calcium; Calcium - antagonists & inhibitors; Calcium - physiology; Calcium Channel Blockers - pharmacology; Calcium Channels - drug effects; Calcium Channels, L-Type; Cell Death; Cell Movement - genetics; Cerebellar Cortex - drug effects; Cerebellar Cortex - pathology; Cerebellar Diseases - genetics; Cerebellar Diseases - metabolism; Cerebellar Diseases - pathology; Cerebellar Diseases - prevention & control; cerebellum; Chelating Agents - pharmacology; Egtazic Acid - analogs & derivatives; Egtazic Acid - pharmacology; ethanol; Ethanol - pharmacology; G Protein-Coupled Inwardly-Rectifying Potassium Channels; granule neurons; Mice; Mice, Neurologic Mutants - genetics; Nerve Tissue Proteins - deficiency; Nerve Tissue Proteins - drug effects; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; Neurites - drug effects; Neurons - drug effects; Neurons - pathology; Neuroprotective Agents - pharmacology; Patch-Clamp Techniques; Potassium Channels - deficiency; Potassium Channels - drug effects; Potassium Channels - genetics; Potassium Channels - physiology; Potassium Channels, Inwardly Rectifying; rescue; Verapamil - pharmacology; weaver
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/(SICI)1097-4547(19970615)48:6<571::AID-JNR10>3.0.CO;2-Y

The mechanisms by which the weaver gene (Reeves et al., 1989; Patil et al., 1995) inhibits neurite extension and/or induces death of the granule neurons in homozygous weaver mouse cerebellum are not presently understood. Here we show that BAPTA‐AM and ethanol, which either reduce cytosolic levels of free calcium or prevent calcium entry, promote neurite outgrowth of the weaver neurons similar to the L‐type calcium channel blocker verapamil (Liesi and Wright, 1996). Importantly, BAPTA‐AM, ethanol, and verapamil not only restore neurite outgrowth of the weaver neurons but adjust their depolarized resting membrane potentials to the levels of normal neurons. These results indicate that calcium‐dependent mechanisms mediate the action of the weaver gene and that the weaver neurons can be normalized by blocking this calcium effect. We further report that BAPTA‐AM and verapamil also have a neuroprotective effect on normal neurons exposed to high concentrations of ethanol. We suggest that verapamil should be evaluated as a drug for treatment of alcohol‐induced brain damage and neurodegenerative disorders. J. Neurosci. Res. 48:571–579, 1997. © 1997 Wiley‐Liss Inc.