Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type K+ Current

doi:10.3390/ijms22031300

. 2021 Jan 28;22(3):1300.

doi: 10.3390/ijms22031300.

Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type K⁺ Current

Yi-Ching Lo^{1

2

3}, Chih-Lung Lin^{4

5}, Wei-Yu Fang¹, Bálint Lőrinczi⁶, István Szatmári⁶, Wan-Hsuan Chang^{1

3}, Ferenc Fülöp^{6

7}, Sheng-Nan Wu^{8

9}

Affiliations

¹ Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
² Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁴ Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
⁵ Department of Neurosurgery, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁶ Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
⁷ MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, Eötvös u. 6, H-6720 Szeged, Hungary.
⁸ Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City 70101, Taiwan.
⁹ Department of Physiology, National Cheng Kung University Medical College, Tainan City 70101, Taiwan.

PMID: 33525680
PMCID: PMC7865226
DOI: 10.3390/ijms22031300

Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type K⁺ Current

Yi-Ching Lo et al. Int J Mol Sci. 2021.

. 2021 Jan 28;22(3):1300.

doi: 10.3390/ijms22031300.

Authors

Yi-Ching Lo^{1

2

3}, Chih-Lung Lin^{4

5}, Wei-Yu Fang¹, Bálint Lőrinczi⁶, István Szatmári⁶, Wan-Hsuan Chang^{1

3}, Ferenc Fülöp^{6

7}, Sheng-Nan Wu^{8

9}

Affiliations

¹ Department of Pharmacology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
² Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁴ Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.
⁵ Department of Neurosurgery, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
⁶ Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
⁷ MTA-SZTE Stereochemistry Research Group, Hungarian Academy of Sciences, Eötvös u. 6, H-6720 Szeged, Hungary.
⁸ Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan City 70101, Taiwan.
⁹ Department of Physiology, National Cheng Kung University Medical College, Tainan City 70101, Taiwan.

PMID: 33525680
PMCID: PMC7865226
DOI: 10.3390/ijms22031300

Abstract

Kynurenic acid (KYNA, 4-oxoquinoline-2-carboxylic acid), an intermediate of the tryptophan metabolism, has been recognized to exert different neuroactive actions; however, the need of how it or its aminoalkylated amide derivative N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide (KYNA-A4) exerts any effects on ion currents in excitable cells remains largely unmet. In this study, the investigations of how KYNA and other structurally similar KYNA derivatives have any adjustments on different ionic currents in pituitary GH₃ cells and hippocampal mHippoE-14 neurons were performed by patch-clamp technique. KYNA or KYNA-A4 increased the amplitude of M-type K⁺ current (I_K(M)) and concomitantly enhanced the activation time course of the current. The EC₅₀ value required for KYNA- or KYNA-A4 -stimulated I_K(M) was yielded to be 18.1 or 6.4 μM, respectively. The presence of KYNA or KYNA-A4 shifted the relationship of normalized I_K(M)-conductance versus membrane potential to more depolarized potential with no change in the gating charge of the current. The voltage-dependent hysteretic area of I_K(M) elicited by long-lasting triangular ramp pulse was observed in GH₃ cells and that was increased during exposure to KYNA or KYNA-A4. In cell-attached current recordings, addition of KYNA raised the open probability of M-type K⁺ channels, along with increased mean open time of the channel. Cell exposure to KYNA or KYNA-A4 mildly inhibited delayed-rectifying K⁺ current; however, neither erg-mediated K⁺ current, hyperpolarization-activated cation current, nor voltage-gated Na⁺ current in GH₃ cells was changed by KYNA or KYNA-A4. Under whole-cell, current-clamp recordings, exposure to KYNA or KYNA-A4 diminished the frequency of spontaneous action potentials; moreover, their reduction in firing frequency was attenuated by linopirdine, yet not by iberiotoxin or apamin. In hippocampal mHippoE-14 neurons, the addition of KYNA also increased the I_K(M) amplitude effectively. Taken together, the actions presented herein would be one of the noticeable mechanisms through which they modulate functional activities of excitable cells occurring in vivo.

Keywords: M-type K+ current; action potential; hippocampal neuron; kynurenic acid; kynurenic acid derivative; pituitary cell.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interests.

Figures

**Figure 1**
Chemical structures of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) and its amide derivatives (KYNA-M1, [3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxylic acid] and KYNA-A4, [N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide]).

**Figure 2**
Effect of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) and N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide (KYNA-A4) on M-type K⁺ current (I_K(M)) recorded from GH₃ cells. In these experiments, we kept cells to be bathed in high-K⁺, Ca²⁺-free solution, and the recording electrode was backfilled with K⁺-containing internal solution. (A) Representative current traces obtained in the control (a), during cell exposure to 10 μM KYNA (b) or 30 μM KYNA (c), and after washout of KYNA (d). The insert shows the voltage-clamp protocol applied, while the dashed line is zero-current level. (B) Concentration-dependent stimulation of KYNA (■) or KYNA-A4 (○) on the amplitude of I_K(M) (i.e., linopirdine-sensitive current) (mean ± SEM; n = 7). Current amplitudes during the exposure to different concentrations (1 μM to 1 mM) of KYNA or KYNA-A4 were taken at the end of the 1-s depolarizing pulse from −50 to −10 mV, and the amplitudes were then compared with those measured after subsequent addition of linopirdine (10 μM). The smooth lines with which the experimental data are overlaid were derived with the goodness-of-fitness test by the modified Hill equation detailed under Section Materials and Methods.

**Figure 3**
Effect of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) and N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide (KYNA-A4) on the activation curve of I_K(M) in GH₃ cells. In this set of current recordings, as the whole-cell mode was firmly established, we voltage-clamped the cell at -50 mV and a series of step commands ranging between -50 and 0 mV in 10-mV increments was applied. The relationship of conductance versus membrane potential was demonstrated in the absence (●) and presence of 30 μM KYNA (∆) or 30 μM KYNA-A4 (□) (mean ± SEM; n = 7). Inset shows the voltage-clamp protocol used.

**Figure 4**
Effect of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) on the voltage-dependent hysteresis of I_K(M) identified from GH₃ cells. Cells were bathed in high-K⁺, Ca²⁺-free solution, and the electrode was backfilled with K⁺-containing solution. (A) Representative current traces in the absence (**left**) or presence of 30 μM KYNA (**right**). Current traces were elicited in response to 3.4-s long isosceles-triangular ramp voltage command (indicated in Inset of the right panel). The dashed arrows in each panel indicate the direction of current trajectory in which time passes (—: forward; —: backward). (B) Summary bar graph depicting the effects of KYNA (10 or 30 μM) or KYNA (30 μM) plus linopirdine (10 μM, Lino) on the ∆area (indicated in the shaded area of (A)) of the voltage hysteresis (mean ± SEM; n = 8 for each bar). * indicates a significant difference from control (p < 0.05) and † indicates significant difference from the KYNA (30 μM) alone group (p < 0.05).

**Figure 5**
Effect of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) on single channel activity of M-type K⁺ (K_M) channels identified in GH₃ cells. In these current recordings, we bathed cells in high-K⁺, Ca²⁺-free solution and the recording electrode was backfilled with low-K⁺ (5.4 mM) solution, the composition of which is stated in Section Materials and Methods. (A) Original single K_M channels obtained in the control (a), during exposure to 10 μM KYNA (b) or 30 μM KYNA (c), and after application of 30 μM KYNA plus 10 μM linopirdine (d). The potential was held at 0 mV relative to the bath. The opening event of the channel is indicated as the upward deflection. (B) Summary bar graph showing effects of KYNA (10 or 30 μM), KYNA (30 μM) plus linopirdine (Lino, 10 μM), KYNA (30 μM) plus bisoprolol (Bis, 10 μM) and KYNA (30 μM) plus dapagliflorizin (Dapa, 10 μM) on the channel opening probability of K_M channels recorded from GH₃ cells (mean ± SEM; n = 7 for each bar). Channel activity was measured at 0 mV relative to the bath. * indicates a significant difference from control (i.e., KYNA was not present) (p < 0.05), while † indicates significant difference from KYNA (30 μM) alone group (p < 0.05).

**Figure 6**
Effect of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) on delayed-rectifier K⁺ current (I_K(DR)) in GH₃ cells. The experiments were undertaken in cells bathed in Ca²⁺-free, Tyrode’s solution, and we filled up the electrode with K⁺-containing solution. (A) Representative current traces obtained in the control (upper) and during cell exposure to 30 μM KYNA. The voltage-clamp profile was demonstrated in the uppermost part. (Ba) Mean *I-V* relations of I_K(DR) taken in the absence (■) and presence (○) of 30 μM KYNA (mean ± SEM; n = 8 for each point). Current amplitude was taken at each depolarizing pulse from a holding potential of −50 mV. Panel (Bb) shows an expanded graph from (Ba), while the arrow indicates a crossover point between these two *I-V* curves.

**Figure 7**
Lack of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) effect of *erg*-mediated K⁺ current (I_K(erg)). In this set of experiments, we kept cells in high-K⁺, Ca²⁺-free solution and the electrode was backfilled with K⁺-containing solution. (A) Representative current traces (i.e., the inwardly directed I_K(erg)) obtained in the control (a) and during exposure to 30 μM KYNA (b) or 30 μM KYNA plus 10 μM E-4031 (c). The upper part shows the voltage-clamp protocol used to evoke I_K(erg). (B) Mean *I-V* relationships of I_K(erg) obtained in the absence (■) of 30 μM KYNA (○) or 30 μM KYNA plus 10 μM E-4031 (∆) (mean ± SEM; n = 7 for each point). Current amplitude was measured at the beginning of each hyperpolarizing pulse. Of notice, the overall *I-V* relationship of I_K(erg) between the absence and presence of KYNA (30 μM) did not differ.

**Figure 8**
Lack of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) effect on the hyperpolarization-activated cation current (I_h) recorded from GH₃ cells. The whole-cell current recordings were conducted in cells bathed in Ca²⁺-free, Tyrode’s solution containing 1 μM TTX and 0.5 mM CdCl₂, and the recording electrode was filled up with K⁺-containing solution. (A) Representative current traces obtained in the control (a, KYNA was not present), and during exposure to KYNA (30 μM) (b) or to KYNA (30 μM) plus cilobradine (Cil, 10 μM) (c). The upper part is the voltage-clamp protocol delivered. (B) Mean *I-V* relationship of I_h taken in the absence (■) and presence of KYNA (30 μM) (○) or KYNA (30 μM) plus cilobradine (Cil, 10 μM) (∆) (mean ± SEM; n = 8 for each point). Current amplitude was taken at the end of 2-s hyperpolarizing pulse to a series of voltages ranging between −110 and −40 mV from a holding potential of −40 mV. Of notice, there is void of KYNA effect on the amplitude or time course of I_h evoked throughout the entire voltage-clamp steps examined; however, further addition of cilobradine, still in the presence of KYNA, can decrease I_h amplitude effectively.

**Figure 9**
Inability of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) to perturb the amplitude or gating of voltage-gated Na⁺ current (I_Na) in GH₃ cells. In these whole-cell experiments, cells were kept to be immersed in Ca²⁺-free, Tyrode’s solution containing 10 mM TEA and 0.5 mM CdCl₂, while we filled up the electrode with Cs⁺-containing internal solution. (A) Representative I_Na traces taken in the control (i.e., KYNA was not present, a) and during cell exposure to 30 μM KYNA (b) or 30 μM KYNA plus 1 μM TTX (c). The voltage-clamp protocol used to elicit I_Na is depicted in the upper part. (B) Summary bar graph showing effects of KYNA, KYNA plus TTX, KYNA plus columbianadin (CBN, 10 μM), or KYNA plus tefluthrin (Tef, 10 μM). Each bar represents the mean ± SEM (n = 7). * indicates a significant difference from KYNA (30 μM) alone group (p < 0.05).

**Figure 10**
Effect of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) and N-(2-(dimethylamino)ethyl)-3-(morpholinomethyl)-4-oxo-1,4-dihydroquinoline-2-carboxamide (KYNA-A4) on spontaneous action potentials (APs) recorded from GH₃ cells. In this set of the experiments, cells were bathed in normal Tyrode’s solution, the electrode was filled with K⁺-containing solution, and the whole-cell current-clamp voltage recordings were performed. (A) Original potential traces obtained in the control (a) and during exposure to 10 μM KYNA (b) or 30 μM KYNA (c). In (B), (Ba) illustrates summary bar graph depicting effects of KYNA (10 or 30 μM), KYNA (30 μM) plus iberiotoxin (Iber, 200 nM), KYNA (30 μM) plus apamin (Apa, 200 nM), and KYNA (30 μM) plus linopirdine (Lino, 10 μM) on the frequency of spontaneous APs in GH₃ cells, while (Bb) shows those of KYNA-A4 (3 or 10 μM), KYNA-A4 (10 μM) plus Iber (200 nM), KYNA-A4 (10 μM) plus Apa (200 nM), and KYNA-A4 (10 μM) plus Lino (10 μM) on firing frequency. Each bar indicates the mean ± SEM (n = 7). * indicates a significant difference from controls (p < 0.05) and † indicates significant difference from KYNA (30 μM) or KYNA-A4 (10 μM) alone group (p < 0.05).

**Figure 11**
Effect of kynurenic acid (KYNA, 4-hydroxyquinoline-2-carboxylic acid) on I_K(M) identified from hippocampal mHippoE-14 neurons. For this set of current recordings, we kept cells immersed in high-K⁺, Ca²⁺-free solution containing 1 μM TTX, and we thereafter backfilled the electrode with K⁺-containing internal solution. (A) Representative current traces activated by membrane depolarization from -50 to -10 mV with a duration of 1 s. The dashed line shows zero-current level. a: control; b: 30 μM KYNA; c: 30 μM KYNA plus 10 μM linopirdine (Lino). (B) Summary bar graph showing effect of KYNA (30 μM) or KYNA (30 μM) plus linopirdine (Lino, 10 μM) on the I_K(M) amplitude recorded from mHippoE-14 neurons (mean ± SEM; n = 7 for each bar). Current amplitudes taken in the absence and presence of KYNA or KYNA plus linopirdine were measured at the end of 1-s depolarizing pulse from −50 to −10 mV. * indicates a significant difference from control (p < 0.05) and † indicates significant difference from KYNA (30 μM) alone group (p < 0.05).

See this image and copyright information in PMC

Cited by

Effective Perturbations by Small-Molecule Modulators on Voltage-Dependent Hysteresis of Transmembrane Ionic Currents.
Wu SN, Wu CL, Cho HY, Chiang CW. Wu SN, et al. Int J Mol Sci. 2022 Aug 21;23(16):9453. doi: 10.3390/ijms23169453. Int J Mol Sci. 2022. PMID: 36012718 Free PMC article. Review.
The Effectiveness in Activating M-Type K⁺ Current Produced by Solifenacin ([(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate): Independent of Its Antimuscarinic Action.
Cho HY, Chuang TH, Wu SN. Cho HY, et al. Int J Mol Sci. 2021 Nov 17;22(22):12399. doi: 10.3390/ijms222212399. Int J Mol Sci. 2021. PMID: 34830281 Free PMC article.
Tryptophan Challenge in Healthy Controls and People with Schizophrenia: Acute Effects on Plasma Levels of Kynurenine, Kynurenic Acid and 5-Hydroxyindoleacetic Acid.
Sathyasaikumar KV, Notarangelo FM, Kelly DL, Rowland LM, Hare SM, Chen S, Mo C, Buchanan RW, Schwarcz R. Sathyasaikumar KV, et al. Pharmaceuticals (Basel). 2022 Aug 15;15(8):1003. doi: 10.3390/ph15081003. Pharmaceuticals (Basel). 2022. PMID: 36015151 Free PMC article.
Evidence for Dual Activation of I_K(M) and I_K(Ca) Caused by QO-58 (5-(2,6-Dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)-1H-pyrazolol[1,5-a]pyrimidin-7-one).
Wu CL, Fu P, Cho HY, Chuang TH, Wu SN. Wu CL, et al. Int J Mol Sci. 2022 Jun 24;23(13):7042. doi: 10.3390/ijms23137042. Int J Mol Sci. 2022. PMID: 35806047 Free PMC article.
Effective Perturbations of the Amplitude, Gating, and Hysteresis of I_K(DR) Caused by PT-2385, an HIF-2α Inhibitor.
Hsiao HT, Lu GL, Liu YC, Wu SN. Hsiao HT, et al. Membranes (Basel). 2021 Aug 17;11(8):636. doi: 10.3390/membranes11080636. Membranes (Basel). 2021. PMID: 34436399 Free PMC article.

See all "Cited by" articles

References

1. Hilmas C., Pereira E.F., Alkondon M., Rassoulpour A., Schwarcz R., Albuquerque E.X. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: Physiopathological implications. J. Neurosci. 2001;21:7463–7473. doi: 10.1523/JNEUROSCI.21-19-07463.2001. - DOI - PMC - PubMed
1. Erhardt S., Olsson S.K., Engberg G. Pharmacological manipulation of kynurenic acid: Potential in the treatment of psychiatric disorders. CNS Drugs. 2009;23:91–101. doi: 10.2165/00023210-200923020-00001. - DOI - PubMed
1. Moroni F., Cozzi A., Sili M., Mannaioni G. Kynurenic acid: A metabolite with multiple actions and multiple targets in brain and periphery. J. Neural Transm. 2012;119:133–139. doi: 10.1007/s00702-011-0763-x. - DOI - PubMed
1. Stone T.W. Does kynurenic acid act on nicotinic receptors? An assessment of the evidence. J. Neurochem. 2020;152:627–649. doi: 10.1111/jnc.14907. - DOI - PMC - PubMed
1. Erhardt S., Schwieler L., Nilsson L., Linderholm K., Engberg G. The kynurenic acid hypothesis of schizophrenia. Physiol. Behav. 2007;92:203–209. doi: 10.1016/j.physbeh.2007.05.025. - DOI - PubMed

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- scite Smart Citations

[1] Hilmas C., Pereira E.F., Alkondon M., Rassoulpour A., Schwarcz R., Albuquerque E.X. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: Physiopathological implications. J. Neurosci. 2001;21:7463–7473. doi: 10.1523/JNEUROSCI.21-19-07463.2001. - DOI - PMC - PubMed

[2] Hilmas C., Pereira E.F., Alkondon M., Rassoulpour A., Schwarcz R., Albuquerque E.X. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: Physiopathological implications. J. Neurosci. 2001;21:7463–7473. doi: 10.1523/JNEUROSCI.21-19-07463.2001. - DOI - PMC - PubMed

[3] Erhardt S., Olsson S.K., Engberg G. Pharmacological manipulation of kynurenic acid: Potential in the treatment of psychiatric disorders. CNS Drugs. 2009;23:91–101. doi: 10.2165/00023210-200923020-00001. - DOI - PubMed

[4] Erhardt S., Olsson S.K., Engberg G. Pharmacological manipulation of kynurenic acid: Potential in the treatment of psychiatric disorders. CNS Drugs. 2009;23:91–101. doi: 10.2165/00023210-200923020-00001. - DOI - PubMed

[5] Moroni F., Cozzi A., Sili M., Mannaioni G. Kynurenic acid: A metabolite with multiple actions and multiple targets in brain and periphery. J. Neural Transm. 2012;119:133–139. doi: 10.1007/s00702-011-0763-x. - DOI - PubMed

[6] Moroni F., Cozzi A., Sili M., Mannaioni G. Kynurenic acid: A metabolite with multiple actions and multiple targets in brain and periphery. J. Neural Transm. 2012;119:133–139. doi: 10.1007/s00702-011-0763-x. - DOI - PubMed

[7] Stone T.W. Does kynurenic acid act on nicotinic receptors? An assessment of the evidence. J. Neurochem. 2020;152:627–649. doi: 10.1111/jnc.14907. - DOI - PMC - PubMed

[8] Stone T.W. Does kynurenic acid act on nicotinic receptors? An assessment of the evidence. J. Neurochem. 2020;152:627–649. doi: 10.1111/jnc.14907. - DOI - PMC - PubMed

[9] Erhardt S., Schwieler L., Nilsson L., Linderholm K., Engberg G. The kynurenic acid hypothesis of schizophrenia. Physiol. Behav. 2007;92:203–209. doi: 10.1016/j.physbeh.2007.05.025. - DOI - PubMed

[10] Erhardt S., Schwieler L., Nilsson L., Linderholm K., Engberg G. The kynurenic acid hypothesis of schizophrenia. Physiol. Behav. 2007;92:203–209. doi: 10.1016/j.physbeh.2007.05.025. - DOI - PubMed

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type K⁺ Current

Affiliations

Effective Activation by Kynurenic Acid and Its Aminoalkylated Derivatives on M-Type K⁺ Current

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

MeSH terms

Substances

Related information

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources