Time-dependent block and resurgent tail currents induced by mouse beta4(154-167) peptide in cardiac Na+ channels

The Journal of General Physiology
Ging Kuo WangSho-Ya Wang

Abstract

Resurgent tail Na(+) currents were first discovered in cerebellar Purkinje neurons. A recent study showed that a 14-mer fragment of a mouse beta4 subunit, beta4(154-167), acts as an intracellular open-channel blocker and elicits resurgent currents in Purkinje neurons (Grieco, T.M., J.D. Malhotra, C. Chen, L.L. Isom, and I.M. Raman. 2005. Neuron. 45:233-244). To explore these phenotypes in vitro, we characterized beta4(154-167) actions in inactivation-deficient cardiac hNav1.5 Na(+) channels expressed in human embryonic kidney 293t cells. Intracellular beta4(154-167) from 25-250 microM elicited a conspicuous time-dependent block of inactivation-deficient Na(+) currents at 50 mV in a concentration-dependent manner. On and off rates for beta4(154-167) binding were estimated at 10.1 microM(-1)s(-1) and 49.1 s(-1), respectively. Upon repolarization, large tail currents emerged with a slight delay at -140 mV, probably as a result of the rapid unblocking of beta4(154-167). Near the activation threshold (approximately -70 mV), resurgent tail currents were robust and long lasting. Likewise, beta4(154-167) induces resurgent currents in wild-type hNav1.5 Na(+) channels, although to a lesser extent. The inactivation peptide acetyl-KIFMK-am...Continue Reading

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Citations

Sep 29, 2011·Cellular and Molecular Life Sciences : CMLS·Mitchell Goldfarb
Jun 27, 2007·Circulation·Argelia Medeiros-DomingoMichael J Ackerman
Aug 13, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Amanda H Lewis, Indira M Raman
Mar 15, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jason S BantIndira M Raman
Sep 27, 2015·Molecular Pain·Cindy BarbosaTheodore R Cummins
Sep 21, 2013·Indian Journal of Psychological Medicine·Yatan Pal Singh Balhara, Shachi Mathur
Aug 31, 2014·The Journal of Physiology·Amanda H Lewis, Indira M Raman
Apr 24, 2014·Anesthesia and Analgesia·Nilufar FoadiJörg Ahrens
Apr 14, 2011·The Journal of Physiology·Angelika Lampert
Jul 10, 2018·Cellular and Molecular Life Sciences : CMLS·Joseph L Ransdell, Jeanne M Nerbonne

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Methods Mentioned

BETA
transfection

Software Mentioned

Axopatch
MATLAB

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