Phospholemman modulates the gating of cardiac L-type calcium channels

Xianming Wang, Guofeng Gao, Kai Guo, Viktor Yarotskyy, Congxin Huang, Keith S. Elmslie, Blaise Z. Peterson

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Ca2+ entry through L-type calcium channels (Cav1.2) is critical in shaping the cardiac action potential and initiating cardiac contraction. Modulation of Cav1.2 channel gating directly affects myocyte excitability and cardiac function. We have found that phospholemman (PLM), a member of the FXYD family and regulator of cardiac ion transport, coimmunoprecipitates with Cav1.2 channels from guinea pig myocytes, which suggests PLM is an endogenous modulator. Cotransfection of PLM in HEK293 cells slowed Cav1.2 current activation at voltages near the threshold for activation, slowed deactivation after long and strong depolarizing steps, enhanced the rate and magnitude of voltage-dependent inactivation (VDI), and slowed recovery from inactivation. However, Ca2+-dependent inactivation was not affected. Consistent with slower channel closing,. PLM significantly increased Ca2+ influx via Cav1.2 channels during the repolarization phase of a human cardiac action potential waveform. Our results support PLM as an endogenous regulator of Cav1.2 channel gating. The enhanced VDI induced by PLM may help protect the heart under conditions such as ischemia or tachycardia where the channels are depolarized for prolonged periods of time and could induce Ca2+ overload. The time and voltage-dependent slowed deactivation could represent a gating shift that helps maintain Ca2+ influx during the cardiac action potential waveform plateau phase.

Original languageEnglish (US)
Pages (from-to)1149-1159
Number of pages11
JournalBiophysical journal
Volume98
Issue number7
DOIs
StatePublished - Apr 7 2010

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L-Type Calcium Channels
Action Potentials
HEK293 Cells
Ion Transport
Cardiac Myocytes
Tachycardia
Muscle Cells
phospholemman
Guinea Pigs
Ischemia

All Science Journal Classification (ASJC) codes

  • Biophysics

Cite this

Wang, X., Gao, G., Guo, K., Yarotskyy, V., Huang, C., Elmslie, K. S., & Peterson, B. Z. (2010). Phospholemman modulates the gating of cardiac L-type calcium channels. Biophysical journal, 98(7), 1149-1159. https://doi.org/10.1016/j.bpj.2009.11.032
Wang, Xianming ; Gao, Guofeng ; Guo, Kai ; Yarotskyy, Viktor ; Huang, Congxin ; Elmslie, Keith S. ; Peterson, Blaise Z. / Phospholemman modulates the gating of cardiac L-type calcium channels. In: Biophysical journal. 2010 ; Vol. 98, No. 7. pp. 1149-1159.
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Wang, X, Gao, G, Guo, K, Yarotskyy, V, Huang, C, Elmslie, KS & Peterson, BZ 2010, 'Phospholemman modulates the gating of cardiac L-type calcium channels', Biophysical journal, vol. 98, no. 7, pp. 1149-1159. https://doi.org/10.1016/j.bpj.2009.11.032

Phospholemman modulates the gating of cardiac L-type calcium channels. / Wang, Xianming; Gao, Guofeng; Guo, Kai; Yarotskyy, Viktor; Huang, Congxin; Elmslie, Keith S.; Peterson, Blaise Z.

In: Biophysical journal, Vol. 98, No. 7, 07.04.2010, p. 1149-1159.

Research output: Contribution to journalArticle

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Wang X, Gao G, Guo K, Yarotskyy V, Huang C, Elmslie KS et al. Phospholemman modulates the gating of cardiac L-type calcium channels. Biophysical journal. 2010 Apr 7;98(7):1149-1159. https://doi.org/10.1016/j.bpj.2009.11.032