Quercetin metabolite 4-methylcatechol does not directly augment the activity of Kv7.4 or Kv7.5

Vascular smooth muscle voltage-gated potassium (Kv) channels, particularly Kv7.4 and Kv7.5 homomers and/or heteromers, are increasingly being recognized to play a role in regulating vascular smooth muscle cell excitability. Thus, augmenting Kv7.4 and Kv7.5 activity to induce vasorelaxation is being investigated as a mechanism for antihypertensive drug development and the underlying molecular mechanism for the antihypertensive effects of dietary components and traditional botanical medicines. Recently, Dias and colleagues wrote that “Dietary polyphenols have been associated with many beneficial cardiovascular effects. However, these effects are rather attributed to small phenolic molecules formed by the gut microbiota…4-Methylcatechol (4-MC) is one such metabolite.” Dias and colleagues demonstrate that 4-MC (15 µM) augments vasorelaxation induced by sodium nitroprusside or forskolin in rat aortic rings. The vasorelaxation was inhibited by pan voltage-gated potassium channel modulator 4-a..., cRNA prepeartion and Two-electrode voltage clamp (TEVC) 
cRNA transcripts encoding human Kv7.4, Kv7.5, Kv1.1, Kv1.2, Kv1.5, and Kv2.1 were generated by in vitro transcription using the mMessage mMachine kit (Thermo Fisher Scientific), after vector linearization, from cDNA sub-cloned into plasmids incorporating Xenopus laevis β-globin 5’ and 3’ UTRs flanking the coding region to enhance translation and cRNA stability.  Defolliculated stage V and VI Xenopus laevis oocytes (Xenoocyte, Dexter, MI, US) were injected with KCNQ cRNAs (0.1-25 ng) and  incubated at 16 oC in ND96 oocyte storage solution containing penicillin and streptomycin, with daily washing, for 1-4 days prior to two-electrode voltage-clamp (TEVC) recording.TEVC was performed at room temperature using an OC-725C amplifier (Warner Instruments, Hamden, CT) and pClamp10 software (Molecular Devices, Sunnyvale, CA) 1-4 days after cRNA injection as described in the section above. For recording, oocytes were placed in a small-volume..., , # Quercetin metabolite 4-methylcatechol does not directly augment the activity of Kv7.4 or Kv7.5

The datasets included are the original Excel files used to generate each panel for figures 1 and 2 in this manuscript. The title of each Excel file is labeled to directly correspond to the figure in the manuscript:

Figure Number & panel > Channel Investigated > Condition > Parameter Measured

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The data contained within this repository are those obtained from cellular electrophysiology recordings. We used two-electrode voltage clamp (TEVC) electrophysiology and the *Xenopus laevis* oocyte expression system to record the electrical activity of wild-type Kv7.4, Kv7.5, Kv7.4/7.5, Kv1.1, Kv1.2, Kv1.5, and Kv2.1 channels in response to 100 uM 4-methylcatechol. *Xenopus laevis* oocytes were injected with cRNA encoding for each of the aforementioned channels and were incubated at 16 degrees for 1-4 days prior to recording using TEVC. The subsequent measurements allow us to charact...