Title: The effect of several putative cognition enhancers on a water maze acquisition deficit produced by pCPA + scopolamine combination treatment Harder JA, Kelly ME Ref: Pharmacol Biochem Behav, 56:657, 1997 : PubMed
A combined treatment of a 3-day regimen of pCPA and low-dose scopolamine produced a significant deficit in the acquisition of a water maze task, which has been suggested as a model for the cognitive deficits of Alzheimer's disease. The putative cognition enhancers oxotremorine, captopril, ondansetron, and tacrine were used in attempts to alleviate the water maze impairment. The effects of oxotremorine were difficult to determine due to nonspecific motor effects causing alterations in swimming speed. No evidence for cognition-enhancing properties of captopril was found. Ondansetron showed a cognition-enhancing effect on one of 4 days, but only at a relatively high dose (1 mg/kg i.p.). Tacrine, however, alleviated the pCPA + scopolamine-induced cognitive deficit. This study may thus provide evidence for the usefulness of tacrine in treating spatial deficits in dementia.
        
Title: Electrophysiological function of the delayed rectifier (IK) in bullfrog sympathetic ganglion neurones Goh JW, Kelly ME, Pennefather PS Ref: Pflugers Arch, 413:482, 1989 : PubMed
Neurones of the bullfrog sympathetic ganglion exhibit at least 5 distinct K+ currents. Two calcium-dependent K+ currents IC and IAHP, the delayed rectifier IK, the muscarinic-sensitive IM and the transient outward current IA. Each current plays a unique role in controlling the shapes and firing patterns of action potentials observed in these neurones. We have found that 3,4-diaminopyridine (DAP) (greater than 0.1 mM) will selectively block IK and IA. Concentrations as high as 2 mM have no effect on IC, IAHP or IM. Since IA is mostly inactivated at resting potentials in these cells, DAP can be used to explore the electrophysiological function of IK. Under normal conditions DAP has no effect on action potential duration or no patterns of repetitive activity. This indicates that IK is normally not involved in modulating these parameters. When IC and IAHP are blocked by removing extracellular calcium, however, inhibition of IK prolongs action potential duration, reduces a fast afterhypolarization and enhances spike frequency adaptation. When IM and IAHP are reduced by barium (1 mM), inhibition of IK by DAP has smaller effects on action potential duration and afterhyperpolarization amplitude, but still enhances spike frequency adaptation. We conclude that electrophysiological effects of blocking IK are critically dependent on the levels of other K+ currents found in these cells.