Selective blockade of the delayed rectifier potassium current by tacrine inDrosophila

✍ Scribed by Kraliz, Derek ;Singh, Satpal

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 212 KB
• Volume: 32
• Category: Article
• ISSN: 0022-3034
• DOI: 10.1002/(sici)1097-4695(199701)32:1<1::aid-neu1>3.0.co;2-d

✦ Synopsis

Tetrahydroaminoacridine (tacrine) increased the duration of the action potentials signifiis an anticholinesterase agent used in the treatment cantly. An interesting aspect of tacrine's selectivity is of Alzheimer's disease. Its effectiveness against dethat the current blocked by it is the quinidine-sensimentia is attributed to its inhibition of acetylcholine tive delayed rectifier K / current rather than the 4breakdown in the synaptic cleft. Tacrine has also been aminopyridine ( 4-AP) -sensitive transient K / current. shown to block ionic currents, including many types This is in contrast to the generally emphasized strucof potassium (K / ) currents, calcium currents, and tural relationship between tacrine and 4-AP. Since sodium currents. However, the physiologic signifitacrine is structurally related to quinidine as well, cance of this blockade, especially with respect to its these observations suggest a structural basis for the effectiveness against Alzheimer's disease, is not clear selectivity of tacrine, 4-AP, and quinidine for specific because of relatively high ( several hundred micromo-K / channels. Furthermore, the data are consistent lar to millimolar) concentrations of tacrine employed with the possibility of increased neurotransmitter in many studies of channel blockade, and because it release, due to prolonged presynaptic action potenblocks several types of currents. A complete mutatials, acting synergistically with the anticholinestertional and pharmacologic resolution of ionic currents ase activity of tacrine to increase its therapeutic in the larval muscles of Drosophila allowed us to exeffectiveness. ᭧ 1997 John Wiley & Sons, Inc. J Neurobiol 32: amine the selectivity of tacrine's effects at very low 1-10, 1997. concentrations. At concentrations as low as 10 mM, Keywords: tacrine; potassium current; Drosophila; actacrine selectively blocked the delayed rectifier K / tion potential; 4-AP current without affecting the three other K / currents