Rivastigmine blocks voltage-activated K+ currents in dissociated rat hippocampal neurons.
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 (IK(A)) and the delayed rectifier K+ current (IK(DR)) in acutely dissociated rat hippocampal pyramidal neurons using the whole-cell patch-clamp technique. Rivastigmine inhibited the amplitudes of IK(A) and IK(DR) in a reversible and concentration-dependent manner. At a concentration of 100 mum, rivastigmine inhibited IK(A) and IK(DR), recorded when the cells were depolarized from -50 to +40 mV, by 65.9 (P<0.01) and 67.3% (P<0.01), respectively. The IC50 values for IK(A) and IK(DR) were 3.8 and 1.7 microM, respectively. The decay time constant of IK(A), recorded following a test pulse to +40 mV, was prolonged reversibly by rivastigmine at concentrations of 10 and 100 microM (both P<0.05). Rivastigmine affected the voltage dependence of IK(A) and IK(DR). At a concentration of 10 mum, it shifted the steady-state inactivation curve of IK(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 IK(DR), 10 microM 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. Our findings that rivastigmine inhibits IK(A) and IK(DR) in rat hippocampal pyramidal neurons suggest that this agent has other pharmacological actions besides its antiacetylcholinesterase activity.
D000818:Animals; D002219:Carbamates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D048448:Phenylcarbamates; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D000068836:Rivastigmine
D002219:Carbamates; D048448:Phenylcarbamates; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D000068836:Rivastigmine