Skip to main content

Regulation of Voltage-gated Potassium (Kv) and Two-Pore Domain Potassium (K2P) Channels implicated in Pulmonary Hypertension

Lee, Mun Ching (2018) Regulation of Voltage-gated Potassium (Kv) and Two-Pore Domain Potassium (K2P) Channels implicated in Pulmonary Hypertension. Doctor of Philosophy (PhD) thesis, University of Kent,. (KAR id:67654)

Language: English
Download (15MB) Preview



Whole-cell patch clamp electrophysiology was used to measure currents of the ion channels expressed in modified tsA-201 cells, in the absence and presence of Nox4 AMIGO and other regulatory molecules. Immunohistochemistry was deployed to visualize the distribution of Kv2.1 and Kv9.3 proteins in the rat lungs and hearts.

Key results and Conclusions

This study supports the findings that Kv9.3 regulates Kv2.1 by increasing the current amplitude, shifting the activation threshold to a more negative voltage range, and prolonging the slow component of time constant of deactivation. These effects could be beneficial in PH as this would mean cells could be brought back to its resting membrane potential faster and the transduction of the next action potential can be delayed. Kv2.1 and Kv9.3 have also been detected at the endothelium and PASMC in rat lungs and hearts, further substantiating the claim that these channels are potential players in regulating PH. AMIGO1 and AMIGO2 proteins are confirmed as regulators of Kv2.1 and Kv9.3 proteins. Nox4 does not regulate Kv2.1, Kv9.3, and TASK-1 channels expressed in tsA-201 cells. While hydrogen peroxide (H2O2) does not have any effect on Kv2.1 and Kv9.3, it abolished the current reduction effect of AMIGO2 on Kv2.1/Kv9.3. Other redox agents used in this study such as dithiothreitol (DTT), 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), and chloramine T (Ch-T) are not modulators of these channels expressed in tsA-201 cells. The lack of effect from Nox4 and these redox agents could suggest that the redox regulation of different Nox subunit/Kv channels combination varies for different cell types due to the different regulatory proteins present in different heterologous expression systems. As with the case of H2O2 and AMIGO2, it is likely that the regulatory proteins, which could facilitate the hypoxia-sensing properties of Nox4 and the effects of the redox agents on the ion channels, are missing in our heterologous expression system, compared with other host cells.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Mathie, Alistair
Uncontrolled keywords: voltage-gated potassium channels, two-pore domain potassium channels, pulmonary hypertension, Kv2.1, Kv9.3, TASK-1, KCNK3, stromatoxin, dithiothreitol, hydrogen peroxide, 5-5’-dithiobis-2-nitrobenzoic acid, chloramine-T, amphoterin-induced gene and open reading frame
Subjects: Q Science
Divisions: Faculties > Sciences > Medway School of Pharmacy
SWORD Depositor: System Moodle
Depositing User: System Moodle
Date Deposited: 17 Jul 2018 11:02 UTC
Last Modified: 23 Jan 2020 04:15 UTC
Resource URI: (The current URI for this page, for reference purposes)
  • Depositors only (login required):


Downloads per month over past year