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Identification of a key residue in Kv7.1 potassium channel essential for sensing external potassium ions.

Wang W, Flores MC, Sihn CR, Kim HJ, Zhang Y, Doyle KJ, Chiamvimonvat N, Zhang XD, Yamoah EN - J. Gen. Physiol. (2015)

Bottom Line: Previous studies have shown that Kv7.1 currents are substantially suppressed by high K(+) e (independent of the effects of altering the electrochemical gradient).Using sequence alignment of S5-pore linkers of several Kv channels, we identified a key residue, E290, found in only a few Kv channels including Kv7.1.We propose that Kv7.1 may use this feedback mechanism to maintain the magnitude of the endocochlear potential, which boosts the driving force to generate the receptor potential of hair cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557.

No MeSH data available.


Related in: MedlinePlus

Modifications of E290C by positively charged MTS reagents decreased the current. (A and B) MTSEA and MTSET modifications of WT hKv7.1 (left) and E290C (right) with 4 mM K+e. MTSEA and MTSET modifications decreased the E290C current but had no appreciable effects on the WT current. (C and D) The current density–voltage relationship of WT and E290C before and after MTSEA (C, n = 7) and MTSET (D, n = 9) modifications. The outward current density was significantly reduced by MTSEA and MTSET modifications (*, P < 0.05). The averaged current density from the last 50 ms of the test pulse was used.
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fig5: Modifications of E290C by positively charged MTS reagents decreased the current. (A and B) MTSEA and MTSET modifications of WT hKv7.1 (left) and E290C (right) with 4 mM K+e. MTSEA and MTSET modifications decreased the E290C current but had no appreciable effects on the WT current. (C and D) The current density–voltage relationship of WT and E290C before and after MTSEA (C, n = 7) and MTSET (D, n = 9) modifications. The outward current density was significantly reduced by MTSEA and MTSET modifications (*, P < 0.05). The averaged current density from the last 50 ms of the test pulse was used.

Mentions: We further hypothesize that restoration of the negative charge at E290C may increase the current amplitude and K+e sensitivity. Therefore, we modified the E290C mutant channel using the negatively charged MTS compound, 2-sulfonatoethyl MTS (MTSES). Modification of E290C by MTSES increased the magnitude of the current, as shown in Fig. 4 (A and C). In contrast, the positively charged MTS reagent 2-aminoethyl MTS (MTSEA) had the opposite effects on the current magnitude (Fig. 5, A and C). To confirm the role of the negative charge at position 290, we used another negatively charged 5-sulfonatopentyl MTS (MTSPeS) and positively charged 2-(trimethylammonium) ethyl MTS (MTSET) to modify E290C and observed similar patterns for the current alteration (Fig. 4, B and D, for MTSPeS and Fig. 5, B and D, for MTSET, respectively). None of these MTS reagents had any appreciable effects on the WT channels (Figs. 4 and 5).


Identification of a key residue in Kv7.1 potassium channel essential for sensing external potassium ions.

Wang W, Flores MC, Sihn CR, Kim HJ, Zhang Y, Doyle KJ, Chiamvimonvat N, Zhang XD, Yamoah EN - J. Gen. Physiol. (2015)

Modifications of E290C by positively charged MTS reagents decreased the current. (A and B) MTSEA and MTSET modifications of WT hKv7.1 (left) and E290C (right) with 4 mM K+e. MTSEA and MTSET modifications decreased the E290C current but had no appreciable effects on the WT current. (C and D) The current density–voltage relationship of WT and E290C before and after MTSEA (C, n = 7) and MTSET (D, n = 9) modifications. The outward current density was significantly reduced by MTSEA and MTSET modifications (*, P < 0.05). The averaged current density from the last 50 ms of the test pulse was used.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4338162&req=5

fig5: Modifications of E290C by positively charged MTS reagents decreased the current. (A and B) MTSEA and MTSET modifications of WT hKv7.1 (left) and E290C (right) with 4 mM K+e. MTSEA and MTSET modifications decreased the E290C current but had no appreciable effects on the WT current. (C and D) The current density–voltage relationship of WT and E290C before and after MTSEA (C, n = 7) and MTSET (D, n = 9) modifications. The outward current density was significantly reduced by MTSEA and MTSET modifications (*, P < 0.05). The averaged current density from the last 50 ms of the test pulse was used.
Mentions: We further hypothesize that restoration of the negative charge at E290C may increase the current amplitude and K+e sensitivity. Therefore, we modified the E290C mutant channel using the negatively charged MTS compound, 2-sulfonatoethyl MTS (MTSES). Modification of E290C by MTSES increased the magnitude of the current, as shown in Fig. 4 (A and C). In contrast, the positively charged MTS reagent 2-aminoethyl MTS (MTSEA) had the opposite effects on the current magnitude (Fig. 5, A and C). To confirm the role of the negative charge at position 290, we used another negatively charged 5-sulfonatopentyl MTS (MTSPeS) and positively charged 2-(trimethylammonium) ethyl MTS (MTSET) to modify E290C and observed similar patterns for the current alteration (Fig. 4, B and D, for MTSPeS and Fig. 5, B and D, for MTSET, respectively). None of these MTS reagents had any appreciable effects on the WT channels (Figs. 4 and 5).

Bottom Line: Previous studies have shown that Kv7.1 currents are substantially suppressed by high K(+) e (independent of the effects of altering the electrochemical gradient).Using sequence alignment of S5-pore linkers of several Kv channels, we identified a key residue, E290, found in only a few Kv channels including Kv7.1.We propose that Kv7.1 may use this feedback mechanism to maintain the magnitude of the endocochlear potential, which boosts the driving force to generate the receptor potential of hair cells.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, School of Medicine, University of Nevada, Reno, Reno, NV 89557.

No MeSH data available.


Related in: MedlinePlus