Skip to main content
SpringerLink
Log in

Intracellular angiotensin (1–7) increases the inward calcium current in cardiomyocytes. On the role of PKA activation

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The influence of intracellular administration of angiotensin (1–7) (Ang 1–7) on the inward calcium current was investigated in myocytes isolated from the left ventricle of Wistar Kyoto rat hearts using the patch-clamp technique. The results indicated: (1) the intracellular administration of Ang (1–7) (100 nM) enhanced the peak inward calcium current (I Ca); (2) the intracellular administration of A779 (100 nM) which a Mas receptor inhibitor, abolished the effect of Ang (1–7) on the calcium current; (3) the activation of PKA and consequent phosphorylation of calcium channels seems to be the mechanism involved in the increment of calcium current induced by the heptapeptide because the intracellular dialysis of the PKA inhibitor suppressed the effect of the heptapeptide; (4) the effect of Ang (1–7) was not related to its secretion into the extracellular space; (5)intracellular dialysis of Ang II (100 nM) has an opposite effect and reduced the peak I Ca; (6) extracellular administration of Ang II (100 nM) to cells previously dialyzed with Ang (1–7) also reduced the peak I Ca previously enhanced by Ang (1–7); and (7) intracellular Ang (1–7) reduced the heart cell volume. Implications for heart contractility were discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. De Mello WC, Frohlich ED (2014) Clinical perspectives and fundamental aspects of local cardiovascular and renal renin-angiotensin systems. Front Endocrinol 5:16. doi:10.3389/fendo.2014.00016

    Google Scholar 

  2. Robertson AL, Khairallah PA (1971) Angiotensin II: rapid localization in nuclei of smooth and cardiac muscle. Science 172:1138–1139

    Article  CAS  PubMed  Google Scholar 

  3. De Mello WC (1994) Is an intracellular renin-angiotensin system involved in control of cell communication in heart? J Cardiovasc Pharmacol 23:640–646

    Article  PubMed  Google Scholar 

  4. De Mello WC (1998) Intracellular angiotensin II regulates the inward calcium current in cardiac myocytes. Hypertension 32(6):976–982

    Article  PubMed  Google Scholar 

  5. De Mello WC (1995) Influence of intracellular renin on heart cell communication. Hypertension 25:1172–1177

    Article  CAS  PubMed  Google Scholar 

  6. De Mello WC (2013) Intracellular renin alters the electrical properties of the intact heart ventricle of adult Sprague Dawley rats. Regul Pept 10(181):45–49. doi:10.1016/j.regpep.2012.12.015 Accessed 11 Jan 2013

    Article  Google Scholar 

  7. Schefe JH, Menk M, Reinemund J, Effertz K, Hobbs RM, Pandolfi PP et al (2006) An novel signal transduction cascade involving direct physical interaction of the renin/prorenin receptor with the transcription factor promyelocytic zinc finger protein. Circ Res 99:1366. doi:10.1161/01.RES.0000251700.00994.0d

    Article  Google Scholar 

  8. De Mello WC (2015) Intracellular renin disrupts chemical communication between heart cells. Pathophysiological implication. Front Endocrinol 5(238):2014. doi:10.3389/fendo.2014.00238 eCollection

    Google Scholar 

  9. De Mello WC, Gerena Y (2008) Eplerenone inhibits the intracrine and extracellular actions of angiotensin II on the inward calcium current in the failing heart. On the presence of an intracrine renin angiotensin aldosterone system. Regul Pept 151:54–60. doi:10.1016/j.regpep.2008.06.003

    Article  PubMed Central  PubMed  Google Scholar 

  10. Re RN (2003) Intracellular renin and the nature of intracrine enzymes. Hypertension 42(2):117–122

  11. Ellis B, Li XC, Miguel-Qin E, Gu V, Zhuo JL (2012) Evidence for a functional intra-cellular angiotensin system in the proximal tubule of the kidney. Am J Physiol Regul Integr Comp Physiol 302:R494–R509

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Gonzalez-Villalobos R, Klassen RB, Allen PL, Johanson K, Baker CB, Kobori H, Navar LG, Hammond TG (2006) Megalin binds and internalizes angiotensin-(1–7). Am J Physiol Renal Physiol 290:F1270–F1275

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Alzayadneh EM, Chappell MC (2014) Nuclear expression of renin-angiotensin system components in NRK-52E renal epithelial cells. J Renin Angiotensin Aldosterone Syst

  14. De Mello WC (2014) Angiotensin (1–7) increases the potassium current and the resting potential of arterial myocytes from vascular resistance vessels of normal adult rats: pathophysiological implications. J Am Soc Hypertens 8(1):14–20. doi:10.1016/j.jash.2013.08.003

    Article  PubMed  Google Scholar 

  15. Nelson MT, Quayle JM (1995) Physiological roles and properties of potassium channels in arterial smooth muscle. Am J Physiol 268:C799–C822

    CAS  PubMed  Google Scholar 

  16. Ferrario CM, Ahmad S, Nagata S, Simington SW, Varagic J, Kon N, Dell’italia LJ (2014) An evolving story of angiotensin-II-forming pathways in rodents and humans. Clin Sci 126:461–469. doi:10.1042/CS20130400

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Gironacci MM, Adamo HP, Corradi G, Santos RA, Ortiz P, Carretero OA (2011) Angiotensin (1–7) induces mas receptor internalization. Hypertension 58:176–181 (Published online before print June 13, 2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Averril DB, Yshiyama Y, Chappell MC, Ferrario CM (2003) Cardiac angiotensin (1–7) in ischemic cardiomyopathy. Circulation 108:2141–2146

    Article  Google Scholar 

  19. De Mello WC, Ferrario CM, Jessup JA (2007) Beneficial versus harmful effects of angiotensin (1–7) on impulse propagation and cardiac arrhythmias in the failing heart. J Renin Angiotensin Aldosterone Syst 8:74–80

    Article  PubMed  Google Scholar 

  20. Santos RAS, Castro CH, Gava E, Pinheiro SVB, Almeida AP et al (2006) Impairment of in vitro and in vivo heart function in angiotensin-(1–7) receptor Mas knockout mice. Hypertension 47:996–1002

    Article  CAS  PubMed  Google Scholar 

  21. De Mello WC (2009) Cell swelling, impulse conduction, and cardiac arrhythmias in the failing heart. Opposite effects of angiotensin II and angiotensin (1–7) on cell volume regulation. Mol Cell Biochem 330:211–217

    Article  PubMed  Google Scholar 

  22. De Mello WC (2014) Angiotensin (1–7) re-establishes heart cell communication previously impaired by cell swelling: implications for myocardial ischemia. Exp Cell Res 323(2):359–365. doi:10.1016/j.yexcr.2014.03.006

    Article  PubMed  Google Scholar 

  23. Almeida PWM, Ri Lima RF, Gomes MER, Resende CR, Campos DRC, Nei A, Gondim AS et al (2013) Functional cross-talk between aldosterone and angiotensin-(1–7) in ventricular myocytes. Hypertension 61:425–430

    Article  PubMed  Google Scholar 

  24. Dias-Peixoto MF, Santos RAS, Gomes ERM, Alves MNM, Almeida PWM, Greco L et al (2008) Molecular mechanisms involved in the angiotensin-(1–7)/Mas signaling pathway in cardiomyocytes. Hypertension 52:542–548

    Article  CAS  PubMed  Google Scholar 

  25. Liu GC, Oudit GY, Fang F, Zhou J, Scholey JW (2012) Angiotensin-(1–7)-induced activation of ERK1/2 is cAMP/protein kinase A-dependent in glomerular mesangial cells. Am J Physiol Renal Physiol 302(6):F784–F790. doi:10.1152/ajprenal.00455.2011 . Accessed 21 Dec 2011

    Article  CAS  PubMed  Google Scholar 

  26. Schwacke JH, Spainhour JC, Ierardi JL, Chaves JM, Arthur JM et al (2013) Network modeling reveals steps in angiotensin peptide processing. Hypertension 61:690–700

    Article  CAS  PubMed  Google Scholar 

  27. Chappell MC (2012) Non classical renin-angiotensin system and renal function. Compr Physiol 2:2733–2752

    PubMed Central  PubMed  Google Scholar 

  28. Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE et al (2002) Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 417:822–828

    Article  CAS  PubMed  Google Scholar 

  29. Mauger JP (2012) Role of the nuclear envelope in calcium signalling. Biol Cell 104(2):70–83. doi:10.1111/boc.201100103

    Article  CAS  PubMed  Google Scholar 

  30. Calaghan SC, Belus A, White E (2003) Do stretch-induced changes in intracellular calcium modify the electrical activity of cardiac muscle? Prog Biophys Mol Biol 82:81–95

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was in part supported by NIH Grant 8G12MD007600.

Author information

Authors and Affiliations

  1. School of Medicine, UPR, Medical Sciences Campus, San Juan, PR, 00936, USA

    Walmor C. De Mello

Authors
  1. Walmor C. De Mello
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Walmor C. De Mello.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

De Mello, W.C. Intracellular angiotensin (1–7) increases the inward calcium current in cardiomyocytes. On the role of PKA activation. Mol Cell Biochem 407, 9–16 (2015). https://doi.org/10.1007/s11010-015-2449-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-015-2449-4

Keywords

Search

Navigation