Open channel block of Kv1.5 currents by citalopram

Lee, Hyang Mi; Hahn, Sang June; Choi, Bok Hee

doi:10.1038/aps.2010.14

Cited by 20 publications

(12 citation statements)

References 36 publications

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“…It has been, however, reported that citalopram may lead to cardiovascular risk, for example QT prolongation, within the clinical concentration range (26), whereas the relation between Kv1.5 inhibition and QT prolongation is not completely clear. The IC 50 value of citalopram for Kv1.5 obtained by the post-ES viability assay (1.5 mM) was comparable to that determined electrophysiologically in the precedent study (2.8 mM) (17) but slightly lower than that obtained electrophysiologically in this study (at the pulse end: 7.48 mM). Taken together, it is notable that citalopram showed Kv1.3 block and the IC 50 s for Kv1.3 were roughly comparable to those for Kv1.5.…”

Section: Discussionsupporting

confidence: 79%

“…Effects of acacetin and citalopram on Kv1.5 channels currents have been reported based on electrophysiological results in a heterologous expression system (17,18). However, the effects were also determined in this study using HEK293 cells heterologously expressing Kv1.5 alone under the same experimental conditions for Kv1.3 channel current measurements in Fig.…”

Section: Effects Of Acacetin and Citalopram On Membrane Currents Thromentioning

confidence: 85%

“…It has been reported that acacetin and citalopram possess inhibitory actions on the Kv1.5 channel (17,18). However, it remains to be determined whether these compounds also affect the Kv1.3 channel or not.…”

Section: Effects Of Acacetin and Citalopram On The Post-es Viability mentioning

confidence: 99%

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New Screening System for Selective Blockers of Voltage-Gated K+ Channels Using Recombinant Cell Lines Dying Upon Single Action Potential

et al. 2013

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Abstract. To develop a simple screening system for blockers of voltage-gated Kv1.3 and Kv1.5 channels, new cell lines co-expressing mutated Nav1.5 (IFM/Q3), K ir 2.1 (Kir), and Kv1.3 or Kv1.5 were introduced as IFM/Q3+Kir+Kv1.3 and IFM/Q3+Kir+Kv1.5, respectively. Electrical stimulation (ES) of a cell line, IFM/Q3+Kir, induced prolonged action potentials due to the slow inactivation of IFM/Q3 and subsequent cell death. Additional co-expression of Kv1.3 or Kv1.5 to IFM/Q3+Kir shortened the evoked action potentials and prevented cell death. In the presence of margatoxin, a selective Kv1.3-blocker, ES induced cell death in IFM/Q3+Kir+Kv1.3, but not in IFM/Q3+Kir+Kv1.5. In the presence of 4-aminopyridine, a non-selective Kv-channel blocker, ES application elicited cell death in both cell lines. The IC 50 s of acacetin, a Kv1.5-blocker, was 10.2 mM in IFM/Q3+Kir+Kv1.3 and almost identical to that in IFM/Q3+Kir+Kv1.5 (7.6 mM). The IC 50 s of citalopram, a 5-HT uptake-inhibitor, were 1.8 mM in IFM/Q3+Kir+Kv1.3 and 1.5 mM in IFM/Q3+Kir+Kv1.5, respectively. These IC 50 s were comparable to those determined electrophysiologically. In conclusion, acacetin and citalopram block both Kv1.3 and Kv1.5 without selectivity. The Kv1.3 or Kv1.5 channel inhibition assay using these new cell lines may be applicable to high-throughput screening because of its simplicity, accuracy, and high costperformance.

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Section: Discussionsupporting

confidence: 79%

Section: Effects Of Acacetin and Citalopram On Membrane Currents Thromentioning

confidence: 85%

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New Screening System for Selective Blockers of Voltage-Gated K+ Channels Using Recombinant Cell Lines Dying Upon Single Action Potential

et al. 2013

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“…, 2004). Similarly, citalopram has been found to inhibit the neuronal Kv 1.5 current (Lee et al. , 2010), the HERG‐K + current (Witchel et al.…”

Section: Discussionmentioning

confidence: 98%

The antidepressant fluoxetine but not citalopram suppresses synapse formation and synaptic transmission between Lymnaea neurons by perturbing presynaptic and postsynaptic machinery

Getz

Zaidi

et al. 2011

Eur J of Neuroscience

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Depression is a debilitating mental disorder, and selective serotonin reuptake inhibitors (SSRIs) constitute the first-line antidepressant treatment choice for the clinical management of this illness; however, the mechanisms underlying their therapeutic actions and side effects remain poorly understood. Here, we compared the effects of two SSRIs, fluoxetine and citalopram, on synaptic connectivity and the efficacy of cholinergic synaptic transmission between identified presynaptic and postsynaptic neurons from the mollusc Lymnaea. The in vitro paired cells were exposed to clinically relevant concentrations of the two SSRIs under chronic and acute experimental conditions, and the incidence of synapse formation and the efficacy of synaptic transmission were tested electrophysiologically and with fluorescent Ca(2+) imaging. We demonstrate that chronic exposure to fluoxetine, but not to citalopram, inhibits synapse formation and reduces synaptic strength, and that these effects are reversible following prolonged drug washout. At the structural level, we demonstrate that fluoxetine, but not citalopram, prevents the expression and localization of the presynaptic protein synaptophysin. Acute exposure to fluoxetine substantially reduced synaptic transmission and synaptic plasticity (post-tetanic potentiation) in established synapses, whereas citalopram reduced synaptic transmission, but not short-term synaptic plasticity. We further demonstrate that fluoxetine, but not citalopram, directly inhibits voltage-gated Ca(2+) currents in the presynaptic neuron, as well as postsynaptic responsiveness to exogenously applied neurotransmitter. This study provides the first direct evidence that fluoxetine and citalopram exert characteristic, non-specific side effects that are unrelated to their function as SSRIs, and that fluoxetine is more detrimental to synaptic physiology and structure than citalopram.

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“…Finally, a number of unrelated compounds, such as CaMK II blockers (2-[N-(2-hydroxyethyl)]-N-(4methoxybenzenesulfonyl)] amino-N-(4-chlorocinnamyl)-N-methylbenzylamine; KN-93), tyrphostin (tyrosine kinase inhibitor, AG-1478), citalopram (antidepressant), disopyramide, cytochalasin (actin-disrupting agent), or loratadine (non-sedating antihistamine), also act directly on Kv1.5 [103][104][105][106][107][108]. However, their pharmacological uses targeting cell proliferation are debatable.…”

Section: Kv15mentioning

confidence: 99%

Targeting the Voltage-Dependent K+ Channels Kv1.3 and Kv1.5 as Tumor Biomarkers for Cancer Detection and Prevention

Felipe¹,

Bielańska

Comes³

et al. 2012

CMC

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Potassium channels (KCh) are a diverse group of membrane proteins that participate in the control of the membrane potential. More than eighty different KCh genes have been identified, which are expressed in virtually all living cells. In addition to nerve and cardiac action potentials, these proteins are involved in a number of physiological processes, including cell volume regulation, apoptosis, immunomodulation and differentiation. Furthermore, many KCh have been reported to play a role in proliferation and cell cycle progression in mammalian cells, and an important number of studies report the involvement of KCh in cancer progression. The voltage dependent potassium (Kv) channels, in turn, form the largest family of human KCh, which comprises about 40 genes. Because Kv1.3 and Kv1.5 channels modulate proliferation of different mammalian cells, these proteins have been analyzed in a number of tumors and cancer cells. In most cancers, the expression patterns of Kv1.3 and Kv1.5 are remodeled, and in some cases, a correlation has been established between protein abundance and grade of tumor malignancy. The list of cancers evaluated is constantly growing, indicating that these proteins may be future targets for treatment. The aim of this review is to provide an updated overview of Kv1.3 and Kv1.5 channels during cancer development. Unlike Kv1.5, Kv1.3 is characterized by a very selective and potent pharmacology, which could lead to specific pharmacological targeting. Because potassium channels may play a pivotal role in tumor cell proliferation, these proteins should be taken into account when designing new cancer treatment strategies.

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Open channel block of Kv1.5 currents by citalopram

Cited by 20 publications

References 36 publications

New Screening System for Selective Blockers of Voltage-Gated K+ Channels Using Recombinant Cell Lines Dying Upon Single Action Potential

New Screening System for Selective Blockers of Voltage-Gated K+ Channels Using Recombinant Cell Lines Dying Upon Single Action Potential

The antidepressant fluoxetine but not citalopram suppresses synapse formation and synaptic transmission between Lymnaea neurons by perturbing presynaptic and postsynaptic machinery

Targeting the Voltage-Dependent K+ Channels Kv1.3 and Kv1.5 as Tumor Biomarkers for Cancer Detection and Prevention

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