Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.1.8 (
cholinesterase
)
12,691
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Galantamine is a
cholinesterase
inhibitor (AChEI) currently used in treatment of Alzheimer's disease (AD). In the present study, the effects of galantamine on currents of cloned
Kv2.1
and Kv1.5 potassium channels were investigated by using patch-clamp whole cell recording techniques.
Kv2.1
and Kv1.5 were stably expressed in HEK293 cells. Galantamine blocked
Kv2.1
current in a concentration-dependent manner. When depolarizing from -50 to +40 mV, the IC50 of galantamine for inhibition of
Kv2.1
was 5.6 microM. Galantamine 10 microM shifted the activation curve of
Kv2.1
to negative potential by 4.0 mV. At the same concentration, galantamine shifted the inactivation curve to negative potential by 25.2 mV. While Kv1.5 was not sensitive to galantamine, Kv1.5 current was not changed by galantamine at concentration of 10 microM. Our data suggest that galantamine potently blocks
Kv2.1
, but not Kv1.5 channels.
...
PMID:Galantamine blocks cloned Kv2.1, but not Kv1.5 potassium channels. 1553 Jun 63
Purpose/Aim
: Besides as a
cholinesterase
(ChE) inhibitor, tacrine is able to act on multiple targets such as nicotinic receptors (nAChRs) and voltage-gated K
+
(Kv) channels.
Kv2.1
, a Kv channel subunit underlying delayed rectifier currents with slow kinetics of inactivation, is highly expressed in the mammalian brain, especially in the hippocampus. Nevertheless, limited data are available concerning the relationship between tacrine and
Kv2.1
channels. In the present study, we explore the possible effects of tacrine on
Kv2.1
channels in heterologous expression systems and N2A cells.
Materials and methods
: The change of expression and currents of
Kv2.1
after treatment with tacrine was detected by PCR and whole-cell recordings, respectively. WST-8 experiments were performed to reveal the effects of tacrine on cell proliferation.
Results
: Incubation with tacrine induced a significant reduction of the mRNA level of
Kv2.1
channels in HEK293 cells. The decline of corresponding currents carried by
Kv2.1
was also observed. Moreover, the proliferation rates of HEK293 cells with
Kv2.1
channel were substantially enhanced after treatment with this chemical for 24 h. Similar results were also detected after exposure to tacrine in N2A cells with native expression of
Kv2.1
channels.
Conclusion
: These lines of evidence indicate that application of tacrine downregulates the expression of
Kv2.1
channels and increase cell proliferation. The effect of tacrine on
Kv2.1
channels may provide an alternative explanation for its neuroprotective action.
...
PMID:Tacrine modulates Kv2.1 channel gene expression and cell proliferation. 3184 45
