Tags

Type your tag names separated by a space and hit enter

Procaine, a state-dependent blocker, inhibits HERG channels by helix residue Y652 and F656 in the S6 transmembrane domain.
J Pharmacol Sci. 2013 Sep 20; 123(1):25-35.JP

Abstract

The article evaluated the inhibitory action of procaine on wild-type and mutated HERG potassium channel current (I(HERG)) to determine whether mutations in the S6 region are important for the inhibition of I(HERG) by procaine. HERG channels (WT, Y652A, and F656A) were expressed in Xenopus laevis oocytes and studied using the standard two-microelectrode voltage-clamp technique. The results revealed that WT HERG is blocked in a concentration-, voltage-, and state-dependent manner by procaine ([IC₅₀] = 34.79 μM). The steady state activation curves slightly move to the negative, while inactivation parameters move to the positive in the presence of procaine. Time-dependent test reveals that voltage-dependent I(HERG) blockade occurs extremely rapidly. Furthermore, the mutation to Ala of Y652 and F656 produce about 11-fold and 18-fold increases in IC₅₀ for I(HERG) blockade, respectively. Simultaneously, for Y652A, the steady state activation and inactivation parameters are shifted to more positive values after perfusion of procaine. Conclusively, procaine state-dependently inhibits HERG channels (WT, Y652A, and F656A). The helix residues Y652 and F656 in the S6 transmembrane domain might play a role in interaction of the drug with the channel.

Authors+Show Affiliations

Cardio-Electrophysiology Research Laboratory, Medical College, Wuhan University of Science and Technology, China.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24005047

Citation

Wang, Na, et al. "Procaine, a State-dependent Blocker, Inhibits HERG Channels By Helix Residue Y652 and F656 in the S6 Transmembrane Domain." Journal of Pharmacological Sciences, vol. 123, no. 1, 2013, pp. 25-35.
Wang N, Ma JH, Zhang PH. Procaine, a state-dependent blocker, inhibits HERG channels by helix residue Y652 and F656 in the S6 transmembrane domain. J Pharmacol Sci. 2013;123(1):25-35.
Wang, N., Ma, J. H., & Zhang, P. H. (2013). Procaine, a state-dependent blocker, inhibits HERG channels by helix residue Y652 and F656 in the S6 transmembrane domain. Journal of Pharmacological Sciences, 123(1), 25-35.
Wang N, Ma JH, Zhang PH. Procaine, a State-dependent Blocker, Inhibits HERG Channels By Helix Residue Y652 and F656 in the S6 Transmembrane Domain. J Pharmacol Sci. 2013 Sep 20;123(1):25-35. PubMed PMID: 24005047.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Procaine, a state-dependent blocker, inhibits HERG channels by helix residue Y652 and F656 in the S6 transmembrane domain. AU - Wang,Na, AU - Ma,Ji Hua, AU - Zhang,Pei Hua, Y1 - 2013/09/03/ PY - 2013/9/6/entrez PY - 2013/9/6/pubmed PY - 2014/4/3/medline SP - 25 EP - 35 JF - Journal of pharmacological sciences JO - J Pharmacol Sci VL - 123 IS - 1 N2 - The article evaluated the inhibitory action of procaine on wild-type and mutated HERG potassium channel current (I(HERG)) to determine whether mutations in the S6 region are important for the inhibition of I(HERG) by procaine. HERG channels (WT, Y652A, and F656A) were expressed in Xenopus laevis oocytes and studied using the standard two-microelectrode voltage-clamp technique. The results revealed that WT HERG is blocked in a concentration-, voltage-, and state-dependent manner by procaine ([IC₅₀] = 34.79 μM). The steady state activation curves slightly move to the negative, while inactivation parameters move to the positive in the presence of procaine. Time-dependent test reveals that voltage-dependent I(HERG) blockade occurs extremely rapidly. Furthermore, the mutation to Ala of Y652 and F656 produce about 11-fold and 18-fold increases in IC₅₀ for I(HERG) blockade, respectively. Simultaneously, for Y652A, the steady state activation and inactivation parameters are shifted to more positive values after perfusion of procaine. Conclusively, procaine state-dependently inhibits HERG channels (WT, Y652A, and F656A). The helix residues Y652 and F656 in the S6 transmembrane domain might play a role in interaction of the drug with the channel. SN - 1347-8648 UR - https://www.unboundmedicine.com/medline/citation/24005047/Procaine_a_state_dependent_blocker_inhibits_HERG_channels_by_helix_residue_Y652_and_F656_in_the_S6_transmembrane_domain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/DN/JST.JSTAGE/jphs/13007FP DB - PRIME DP - Unbound Medicine ER -