Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.
SK channels are small conductance, Ca(2+)-activated K(+) channels that underlie neuronal slow afterhyperpolarization and mediate spike frequency adaptation. Using the patch clamp technique, we tested the effects of eight clinically relevant psychoactive compounds structurally related to the tricyclic antidepressants, on SK2 subtype channels cloned from rat brain and functionally expressed in the human embryonic kidney cell line, HEK293. Amitriptyline, carbamazepine, chlorpromazine, cyproheptadine, imipramine, tacrine and trifluperazine blocked SK2 channel currents with micromolar affinity. The block was reversible and concentration-dependent. The potency differed according to chemical structure. In contrast, the cognitive enhancer linopirdine was ineffective at blocking these channels. Our results point to a distinct pharmacological profile for SK channels.
Department of Anesthesia and Critical Care, University of Chicago, 5841 S. Maryland Ave., Box 4028, 60637, Chicago, IL, USA.
J C
JC
Dreixler
J
J
Bian
Y
Y
Cao
M T
MT
Roberts
J D
JD
Roizen
K M
KM
Houamed
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D004274:DNA, Recombinant / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D003868:Dequalinium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels
D000929:Antidepressive Agents, Tricyclic; D004274:DNA, Recombinant; D007211:Indoles; C496897:KCNN2 protein, human; C496899:Kcnn2 protein, rat; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011725:Pyridines; D051640:Small-Conductance Calcium-Activated Potassium Channels; D003868:Dequalinium; C061017:linopirdine