Serotonin depolarizes the membrane potential in rat mesenteric artery myocytes by decreasing voltage-gated K+ currents

Bae, Young Min; Kim, Aeran; Kim, Junghwan; Park, Sang Woong; Kim, Tae‐Kyung; Lee, Youn-Ri; Kim, Bokyung; Cho, Sung-Il

doi:10.1016/j.bbrc.2006.06.116

Cited by 57 publications

(68 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fifth, serotonin acts as vasoconstrictor and was reported to inhibit Kv channels in vascular smooth muscle. 20) Although SSRIs may increase the serotonin concentration in the circulation, thereby increasing cardiovascular risk in specific hypertensive patients, 21) this increase in serotonin by SSRIs was not possible in a single cell experimental system. Therefore, the inhibition of Kv current by fluvoxamine was not due to SSRI-induced increases .…”

Section: Discussionmentioning

confidence: 99%

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K<sup>+</sup> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Hong

Kim

et al. 2015

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

We demonstrated the inhibitory effect of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), on voltage-dependent K (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells using a whole-cell patch clamp technique. Fluvoxamine reduced the amplitude of Kv currents in a concentration-dependent manner with an IC 50 value of 3.71 1.09 µM and a Hill coefficient of 0.62 0.14. Although fluvoxamine did not significantly affect the steady-state activation curve, it shifted the steady-state inactivation curve toward a more negative potential. Pretreatment with another SSRI, paroxetine, did not affect the basal Kv current and did not alter the inhibitory effect of fluvoxamine on Kv channels. We concluded that fluvoxamine inhibits the Kv current in a concentration-dependent manner and in a closed (inactivated) state of the Kv channels independent of serotonin reuptake inhibition.Key words fluvoxamine;voltage-dependentK + channel; coronary artery; smooth muscle; selective serotonin reuptake inhibitorFluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been used for the treatment of major depression, anxiety, and panic disorder since 1983 in many countries, including those in Europe and Japan.1,2) The antidepressant activity of fluvoxamine is derived from inhibition of serotonin reuptake in the central nervous system with negligible effects on other neurotransmitter reuptake systems.3,4) A recent study indicated that fluvoxamine showed high affinity for the σ1 receptor, which has a neuromodulatory role on the neurotransmitter system and an antidepressant-like effect. 5-7)Although fluvoxamine has beneficial effects in the treatment of depression, its administration is associated with common side effects, including nausea, anorexia, palpitations, headache, and dizziness. 8)Fluvoxamine also affects ion channels, such as the human ether-a-go-go related (hERG) K + and Kv1.5 channels. 9,10) However, these studies were performed primarily in cultured cell lines rather than in native cells. Therefore, questionsremainabouttheeffectoffluvoxamineonionchannels from freshly isolated cells, particularly vascular smooth muscle cells. 11,12) Our previous reports suggested that Kv channels participate in the regulation of resting membrane potential and thus resting tone in some arteries. 13,14) In addition, pathological states such as hypertension, diabetes, and hypoxia, are closely related with alteration of Kv channel activity and expression in the vasculature.15) Therefore, the adverse effects of drugs on Kv channels should be clearly determined to correctly interpret experimental data regarding vascular disorders.Considering the usefulness of fluvoxamine as a SSRI and the physiological importance of Kv channels, the effects of fluvoxamine on vascular Kv channel should be clearly examined to avoid toxic effect on the vasculature when applying fluvoxamineasantidepressantdrug.In the present study, we investigated the effects of fluvoxamine on Kv channels using freshly isolated coronary ...

show abstract

Section: Discussionmentioning

confidence: 99%

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K<sup>+</sup> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Hong

Kim

et al. 2015

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…In systemic arteries, many reports suggest that the KV current, although the molecular identity seems to be heterogeneous and is still controversial, is important in the regulation of smooth muscle Em and vascular tone, and thus peripheral resistance. KV channels are the target of many vasoactive agonists, including 5-HT (Cogolludo et al, 2003;Cole et al, 2005;Bae et al, 2006), and the functional down-regulation of these channels has been observed in many types of hypertension (Yuan et al, 1998;Jackson, 2005). The concept that KV channels regulate vasoconstriction via Em regulation is shown schematically in Fig.…”

Section: Ion Channels In Vascular Smooth Muscle and Blood Pressurementioning

confidence: 99%

“…The mesenteric blood flow is controlled by the mesenteric vascular resistance, and Em regulation by K + currents in mesenteric myocytes is important in mesenteric vascular resistance (Nelson et al, 1990;Cox et al, 2001;Ghisdal et al, 2001). Bae et al (2006) recently demonstrated that the Em of mesenteric artery myocytes is under the regulation of KV currents and that the KV channels are the major target of vasoactive agonist-induced Em depolarization in rat mesenteric artery smooth muscle cells (MASMCs). Data in Figs.…”

Section: Ion Channels Of Mesenteric Artery Smooth Muscle and Mesentermentioning

confidence: 99%

“…Interestingly, the blockade of KV channels by 4-aminopyridine (4-AP) in mesenteric arterial myocytes induced an anorexic effect similar to that with an SSRI and fenfluramine (McDaniel et al, 2001). It should be noted that 5-HT, whose concentration is an important regulator of appetite in the CNS, potently decreases KV currents in mesenteric artery myocytes and causes Em depolarization like 4-AP (Bae et al, 2006). This may indicate that 5-HT can cause an anorexic effect by a non-neuronal (vascular) mechanism as well as acting as an anorexic neurotransmitter in the CNS.…”

Section: Ion Channels Of Mesenteric Artery Smooth Muscle and Mesentermentioning

confidence: 99%

See 1 more Smart Citation

Serotonin-induced ion channel modulations in mesenteric artery myocytes from normotensive and DOCA-salt hypertensive rats

Bae

Sung

Noh

et al. 2007

J. Smooth Muscle Res.

Self Cite

View full text Add to dashboard Cite

Although serotonin (5-hydroxytryptamine, 5-HT) has been found to be a potent vasoconstrictor, a pivotal role of 5-HT in the control of appetite and mood control by the modulation of neuronal synapse has also been proposed. Selective 5-HT reuptake inhibitors (SSRIs) are frequently used to suppress appetite and treat depressive disorder, and the target protein of SSRIs is the 5-HT transporter (5-HTT) in the neuronal synapse. However, SSRIs may increase the free 5-HT concentration in circulating blood because platelets and vascular smooth muscles express functional 5-HTT. In addition, enhanced vasoactive action of 5-HT and alterations in 5-HT receptor subtypes have been reported in some types of hypertension. Therefore, we can infer that the use of drugs such as SSRIs in some hypertensive patients is potentially risky. Altered functional expression of ion channels in vascular smooth muscle is suggested to be a mechanism for the enhanced vasoconstriction by vasoactive agonists, including 5-HT. In this brief review, we compared the electrophysiological properties of mesenteric artery myocytes and their modulation by 5-HT between sham-operated control and deoxycorticosterone acetate (DOCA)-salt hypertensive rats.

show abstract

“…Inhibition of the Kv channels by 4-aminopyridine causes the depolarization and vasoconstriction in various arteries (11,12). Given the usefulness of YC-1 and the physiological importance of Kv channels in the vascular system, a thorough understanding of all of the actions of YC-1 on Kv channels is essential for the accurate interpretation of experimental results obtained using this substance.…”

Section: Introductionmentioning

confidence: 99%

The Guanylyl Cyclase Activator YC-1 Directly Inhibits the Voltage-Dependent K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Park

et al. 2010

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. We investigated the effects of YC-1, an activator of soluble guanylyl cyclase (sGC), on voltage-dependent K + (Kv) channels in smooth muscle cells from freshly isolated rabbit coronary arteries by using the whole-cell patch clamp technique. YC-1 inhibited the Kv current in a dose-dependent fashion with an apparent K d of 9.67 μ M. It accelerated the decay rate of Kv channel inactivation without altering the kinetics of current activation. The rate constants of association and dissociation for YC-1 were 0.36 ± 0.01 μ M , respectively. YC-1 did not have a significant effect on the steady-state activation and inactivation curves. The recovery time constant from inactivation was decreased in the presence of YC-1, and application of train pulses (1 or 2 Hz) caused a progressive increase in the YC-1 blockade, indicating that YC-1-induced inhibition of Kv currents is use-dependent. Pretreatment with Bay 41-2272 (also a sGC activator), ODQ (a sGC inhibitor), or Rp-8-Br-PET-cGMPs (a protein kinase G inhibitor) did not affect the basal Kv current and also did not significantly alter the inhibitory effect of YC-1. From these results, we suggest that YC-1 directly inhibits the Kv current independently of sGC activation and in a state-, time-, and use-dependent fashion.

show abstract

Serotonin depolarizes the membrane potential in rat mesenteric artery myocytes by decreasing voltage-gated K+ currents

Cited by 57 publications

References 32 publications

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K<sup>+</sup> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K<sup>+</sup> Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Serotonin-induced ion channel modulations in mesenteric artery myocytes from normotensive and DOCA-salt hypertensive rats

The Guanylyl Cyclase Activator YC-1 Directly Inhibits the Voltage-Dependent K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

Contact Info

Product

Resources

About