Rivastigmine blocks voltage-activated K + currents in dissociated rat hippocampal neurons

Abstract

1. Rivastigmine is an acetylcholinesterase inhibitor used in Alzheimer's disease therapy. In the present study, we investigated the effects of rivastigmine on the transient outward K + current (I K(A)) and the delayed rectifier K + current (I K(DR)) in acutely dissociated rat hippocampal pyramidal neurons using the whole-cell patch-clamp technique. 2. Rivastigmine inhibited the amplitudes of I K(A) and I K(DR) in a reversible and concentration-dependent manner. At a concentration of 100 μM, rivastigmine inhibited I K(A) and I K(DR), recorded when the cells were depolarized from -50 to +4OmV, by 65.9 (P<0.01) and 67.3% (P<0.01), respectively. The IC 50 values for I K(A) and I K(DR) were 3.8 and 1.7 μM, respectively. 3. The decay time constant of I K(A), recorded following a test pulse to +40 mV, was prolonged reversibly by rivastigmine at concentrations of 10 and 100 μM (both P<0.05). 4. Rivastigmine affected the voltage dependence of I K(A) and I K(DR). At a concentration of 10 μM, it shifted the steady-state inactivation curve of I K(A) towards more negative potentials by -11 mV (P<0.05), but had no effect on the steady-state activation curve or the recovery from inactivation. Regarding the kinetic properties of I K(DR), 10 μM rivastigmine shifted the steady-state activation and inactivation curves towards more negative potentials by -10 (P<0.05) and -27 mV (P<0.01), respectively. 5. Our findings that rivastigmine inhibits I K(A) and I K(DR) in rat hippocampal pyramidal neurons suggest that this agent has other pharmacological actions besides its antiacetylcholinesterase activity.