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L-type calcium channel current up-regulation by chronic stress is associated with increased α1c subunit expression in rat ventricular myocytes

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Cell Stress and Chaperones Aims and scope

Abstract

The L-type calcium channel plays a pivotal role in the regulation of a wide range of cellular processes, including membrane excitability, Ca2+ homeostasis, protein phosphorylation, and gene regulation. Alterations in the density or function of the L-type calcium channel have been implicated in a variety of cardiovascular diseases. Our previous study found that acute restraint stress could cause an enhancement of the L-type calcium current (I Ca-L), which correlated with an up-regulation of activation characters of the calcium channel. In this study, we observed the change of I Ca-L in rat ventricular myocytes under chronic restraint stress using the whole-cell patch-clamp technique and further explored its modulation mechanisms. The results showed that chronic restraint stress could also enhance I Ca-L, but increased I Ca-L was not accompanied by an alteration of the characteristics of activation and inactivation of the L-type calcium channel. Furthermore, results from reverse-transcription polymerase chain reaction and Northern blot showed that the abundance of α1c subunit messenger RNA of the L-type calcium channel in the ventricle was increased significantly after chronic stress, and Western blot analysis revealed the amount of α1c subunit protein also was elevated. These results suggest that the L-type calcium channel is involved in stress-induced cardiomyocyte injury, and the up-regulated expression of the L-type calcium channel α1c subunit might contribute to the I Ca-L change under chronic stress, which is different from the regulation mechanism of acute restraint stress that mostly relates to an alteration in protein kinase A-dependent channel activation. Thus, it would provide a new insight into the mechanism of cardiomyocyte injury induced by stress.

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Abbreviations

I Ca-L :

L-type calcium current

RT-PCR:

reverse-transcription polymerase chain reaction

PKA/C:

protein kinase A /C

[Ca2+]i :

intracellular calcium

ER:

endoplasmic reticulum

NE:

norepinephrine

References

  • Aggarwal R, Boyden PA (1995) Diminished calcium and barium currents in myocytes surviving in the epicardial border zone of the 5-day infracted canine heart. Circ Res 77:1180–1191

    PubMed  CAS  Google Scholar 

  • Balke CW, Shorofsky SR (1998) Alterations in calcium handling in cardiac hypertrophy and heart failure. Cardiovasc Res 37:290–299

    Article  PubMed  CAS  Google Scholar 

  • Bean BP (1985) Two kinds of calcium channels in canine atrial cells. J Gen Physiol 86:1–30

    Article  PubMed  CAS  Google Scholar 

  • Berridge MJ, Lipp P, Bootman MD (2000) The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol 1:11–21

    Article  PubMed  CAS  Google Scholar 

  • Bers DM (1991) Ca influx via sarcolemmal Ca channels. In: Bers DM (ed) Excitation-contraction coupling and cardiac contractile force. Kluwer, Norwell, MA, pp 49–70

    Google Scholar 

  • Bers DM (2002) Cardiac excitation–contraction coupling. Nature 415:198–205

    Article  PubMed  CAS  Google Scholar 

  • Bodi I, Mikala G, Koch SE, Akhter SA, Schwartz A (2005) The L-type calcium channel in the heart: the beat goes on. J Clin Invest 115:3306–3317

    Article  PubMed  CAS  Google Scholar 

  • Brosenitsch TA, Salgado Commissariat D, Kunze DL, Katz DM (1998) A role for L-type calcium channels in developmental regulation of transmitter phenotype in primary sensory neurons. Neurosci 18:1047–1055

    CAS  Google Scholar 

  • Campbell DL, Strauss HC (1995) Regulation of calcium channels in the heart. Adv Second Messenger Phosphoprot Res 30:25–88

    CAS  Google Scholar 

  • Catterall WA (1995) Structure and function of voltage-gated ion channels. Annu Rev Biochem 64:493–501

    Article  PubMed  CAS  Google Scholar 

  • Catterall WA (2000) Structure and regulation of voltage-gated Ca2+ channels. Annu Rev Cell Dev Biol 16:521–555

    Article  PubMed  CAS  Google Scholar 

  • Christ T, Boknik P, Wöhrl S et al (2004) L-type Ca2+ current downregulation in chronic human atrial fibrillation is associated with increased activity of protein phosphatases. Circulation 110:2651–2657

    Article  PubMed  CAS  Google Scholar 

  • Communal C, Singh K, Pimentel DR, Colucci WS (1998) Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 98:1329–1334

    PubMed  CAS  Google Scholar 

  • Das DK, Engelman RM, Maulik N (1999) Oxygen free radical signaling in ischemic preconditioning. In: Das DK (ed) Heart in stress . Ann NY Acad Sci 874:49–65

  • Demaurex N, Distelhorst C (2003) Apoptosis—the calcium connection. Science 300:65–67

    Article  PubMed  CAS  Google Scholar 

  • Feuerstein GZ, Young PR (2000) Apoptosis in cardiac diseases: stress- and mitogen-activated signaling pathways. Cardiovasc Res 45:560–569

    Article  PubMed  CAS  Google Scholar 

  • Galea LAM, Mcewen BS, Tanapat P et al (1997) Sex differences in dendritic atrophy of CA3 pyramidal neurons in response to chronic restraint stress. Neurosci 81:689–697

    Article  CAS  Google Scholar 

  • Gao F, Gong B, Christopher TA, Lopez BL, Karasawa A, Ma XL (2001) Anti-apoptotic effect of benidipine, a long-lasting vasodilating calcium antagonist, in ischaemic/reperfused myocardial cells. Br J Pharmacol 132:869–878

    Article  PubMed  CAS  Google Scholar 

  • Goldenberg I, Grossman E, Jacobson KA, Shneyvays V, Shainberg A (2001) Angiotensin II-induced apoptosis in rat cardiomyocyte culture: a possible role of AT1 and AT2 receptors. J Hypertens 19:1681–1689

    Article  PubMed  CAS  Google Scholar 

  • Hajnoczky G, Csordas G, Madesh M, Pacher P (2000) Control of apoptosis by IP3 and ryanodine receptor driven calcium signals. Cell Calcium 28:349–363

    Article  PubMed  CAS  Google Scholar 

  • Herzig S, Neumann J (2000) Effects of serine/threonine protein phosphatases on ion channels in excitable membranes. Physiol Rev 80:173–210

    PubMed  CAS  Google Scholar 

  • Isenberg G, Klockner U (1982) Calcium tolerant ventricular myocytes prepared by preincubation in a “KB” medium. Pflugers Arch 395:6–18

    Article  PubMed  CAS  Google Scholar 

  • Kamp TJ, Hell JW (2000) Regulation of L-type calcium channels by protein kinase A and protein kinase C. Circ Res 22:1095–1102

    Google Scholar 

  • Klockner U, Isenberg G (1994) Intracellular pH Modulates the Availability of Vascular L-type Ca2+ Channels. J Gen Physiol 103:647–663

    Article  PubMed  CAS  Google Scholar 

  • Marty A, Neher E (1995) Tight-seal whole-cell recording. In: Sakmann B, Neher E (eds) Single-channel recording, 2nd edn. Plenum, New York, pp 31–52

    Google Scholar 

  • Moosmang S, Lenhardt P, Haider N, Hofmann F, Wegener JW (2005) Mouse models to study L-type calcium channel function. Pharmacol Ther 106:347–355

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee R, Spinale FG (1998) L-type calcium channel abundance and function with cardiac hypertrophy and failure: A review. J Mol Cell Cardiol 30:1899–1916

    Article  PubMed  CAS  Google Scholar 

  • Muth JN, Bodi I, Lewis W, Varadi G, Schwartz A (2001) A Ca2+-dependent transgenic model of cardiac hypertrophy: A role for protein kinase Calpha. Circulation 103:140–147

    PubMed  CAS  Google Scholar 

  • Schultz D, Mikala G, Yatani A et al (1993) Cloning, chromosomal localization, and functional expression of the 1 subunit of the L-type voltage-dependent calcium channel from normal human heart. Proc Natl Acad Sci USA 90:6228–6232

    Article  PubMed  CAS  Google Scholar 

  • Schwartz AR, Gerin W, Davidson KW, Picking TG, Brosschot JF, Thayer JF, Christenfeld N, Linden W (2003) Toward a causal model of cardiovascular responses to stress and the development of cardiovascular disease. Psychosom Med 65:22–35

    Article  PubMed  Google Scholar 

  • Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ (2003) BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science 300:135–159

    Article  PubMed  CAS  Google Scholar 

  • Timothy JK, He JQ (2002) L-type Ca2+ channels gaining respect in heart failure. Cardiovasc Res 91:451–453

    Google Scholar 

  • Trump BF, Berezesky IK (1995) Calcium-mediated cell injury and cell death. FASEB 9:219–228

    CAS  Google Scholar 

  • Van Wagoner DR, Pond AL, Lamorgese M, Rossie SS, McCarthy PM, Nerbonne JM (1999) Atrial L-type Ca2+ currents and human atrial fibrillation. Circ Res 85:428–436

    PubMed  Google Scholar 

  • Xu J, Ma Q, Duan HF, Qian LJ (2003) Effects of stress on L-type calcium channels of rat ventricular myocytes. Chin J Applied Physiol 19:216–219

    CAS  Google Scholar 

  • Yue L, Feng J, Gaspo R, Li GR, Wang Z, Nattel S (1997) Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation. Circ Res 81:512–525

    PubMed  CAS  Google Scholar 

  • Zhao Y, Wang WY, Qian LJ (2007) Hsp70 may protect cardiomyocytes from stress -induced injury by inhibiting Fas-mediated apoptosis. Cell Stress Chaperones 12:83–95

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (NNSFC; 30430590) and the National High Technology Research Development Program of China (2006AA02Z4C8).

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Authors and Affiliations

  1. Laboratory of Stress Medicine, Institute of Health and Environmental Medicine, Da-li Road 1, Tianjin, 300050, China

    Yun Zhao, Jun Xu, JingBo Gong & LingJia Qian

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  1. Yun Zhao
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  2. Jun Xu
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  3. JingBo Gong
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  4. LingJia Qian
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Correspondence to LingJia Qian.

Additional information

Y. Zhao and J. Xu contributed equally to this work.

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Zhao, Y., Xu, J., Gong, J. et al. L-type calcium channel current up-regulation by chronic stress is associated with increased α1c subunit expression in rat ventricular myocytes. Cell Stress and Chaperones 14, 33–41 (2009). https://doi.org/10.1007/s12192-008-0052-2

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  • DOI: https://doi.org/10.1007/s12192-008-0052-2

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