ABSTRACT
<p><b>AIM</b>To study the effects of tacrine on IK and IA potassium current in primary cultured rat hippocampal neurons.</p><p><b>METHODS</b>Whole cell patch clamp and primary rat hippocampal neuron cultures were used.</p><p><b>RESULTS</b>Tacrine was shown to reduce the amplitude of IK and IA, in concentration-dependent manners. The IC50s at +40 mV for reduction of IK and IA were 23 and 52.6 mumol.L-1, respectively. Tacrine (30 mumol.L-1) shifted the steady state activation of IK and IA to negative potentials by 12 and 15 mV, respectively. The V1/2 of activation curves for IK current before and after the application of tacrine were (6.7 +/- 1.4) mV and (-5.4 +/- 1.3) mV, respectively. The k of activation curves for IK current was 13.4 + 1.3 and 12.5 + 1.4 without and with tacrine, respectively. The V1/2 of activation curve for IA current were (-9.9 +/- 2.6) mV and (-24 +/- 5) mV in the absence and presence of tacrine, respectively, and the k value was not changed.</p><p><b>CONCLUSION</b>Tacrine inhibited IK and IA currents in rat hippocampal neurons and it is more potent for blocking IK.</p>
Subject(s)
Animals , Female , Male , Rats , Animals, Newborn , Cells, Cultured , Cholinesterase Inhibitors , Pharmacology , Hippocampus , Cell Biology , Physiology , Neurons , Cell Biology , Physiology , Patch-Clamp Techniques , Potassium Channels , Potassium Channels, Inwardly Rectifying , Rats, Wistar , Tacrine , PharmacologyABSTRACT
The present study was carried out to determine the functional properties of Kv4.2 expressed in mammalian cells in comparison with native transient potassium outward current (I(A)) in the hippocampal neurons. Transient transfection, cell culture and whole cell voltage clamp techniques were used. The results showed that I(A) in cultured rat hippocampal neurons and Kv4.2 expressed in HEK293 cells both displayed "A"-type current properties. The activation curves of I(A) and Kv4.2 were better fitted by simple Boltzmann function with V(1/2) 10.0+/-3.3 mV, k 13.9+/-2.6 mV for I(A) and V1/2 -9.7+/-4.1 mV, k 15.8+/-5.7 mV for Kv4.2, respectively. The steady-state inactivation curves of I(A) had a midpoint of -93.0+/-11.4 mV and a slope of 9.0+/-1.5 mV. The voltage-dependence of inactivation for Kv4.2 exhibited midpoint and slope values of -59.4+/-12.2 mV and 8.0+/-3.1 mV, respectively. The time constants (tau) of recovery from inactivation of I(A) and Kv4.2 were 27.9+/-14.1 ms and 172.8+/-10.0 ms, respectively. These results suggest that Kv4.2 is probably a major isoform contributing to I(A) in hippocampus neurons.