Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing

E. R. Pfeiffer, A. T. Wright, A. G. Edwards, J. C. Stowe, K. McNall, J. Tan, I. Niesman, H. H. Patel, D. M. Roth, J. H. Omens, A. D. McCulloch

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Mechanical stretch of cardiac muscle modulates action potential propagation velocity, causing potentially arrhythmogenic conduction slowing. The mechanisms by which stretch alters cardiac conduction remain unknown, but previous studies suggest that stretch can affect the conformation of caveolae in myocytes and other cell types. We tested the hypothesis that slowing of action potential conduction due to cardiac myocyte stretch is dependent on caveolae.Cardiac action potential propagation velocities, measured by optical mapping in isolated mouse hearts and in micropatterned mouse cardiomyocyte cultures, decreased reversibly with volume loading or stretch, respectively (by 19. ±. 5% and 26. ±. 4%). Stretch-dependent conduction slowing was not altered by stretch-activated channel blockade with gadolinium or by GsMTx-4 peptide, but was inhibited when caveolae were disrupted via genetic deletion of caveolin-3 (Cav3 KO) or membrane cholesterol depletion by methyl-β-cyclodextrin. In wild-type mouse hearts, stretch coincided with recruitment of caveolae to the sarcolemma, as observed by electron microscopy. In myocytes from wild-type but not Cav3 KO mice, stretch significantly increased cell membrane capacitance (by 98. ±. 64%), electrical time constant (by 285. ±. 149%), and lipid recruitment to the bilayer (by 84. ±. 39%).Recruitment of caveolae to the sarcolemma during physiologic cardiomyocyte stretch slows ventricular action potential propagation by increasing cell membrane capacitance.

Original languageEnglish (US)
Pages (from-to)265-274
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume76
DOIs
StatePublished - Nov 1 2014
Externally publishedYes

Fingerprint

Caveolae
Muscle Cells
Action Potentials
Cardiac Myocytes
Sarcolemma
Caveolin 3
Cell Membrane
Gadolinium
Cyclodextrins
Myocardium
Electron Microscopy
Cholesterol
Lipids
Peptides
Membranes

Keywords

  • Capacitance
  • Cardiac mechanoelectric feedback
  • Caveolae

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing. / Pfeiffer, E. R.; Wright, A. T.; Edwards, A. G.; Stowe, J. C.; McNall, K.; Tan, J.; Niesman, I.; Patel, H. H.; Roth, D. M.; Omens, J. H.; McCulloch, A. D.

In: Journal of Molecular and Cellular Cardiology, Vol. 76, 01.11.2014, p. 265-274.

Research output: Contribution to journalArticle

Pfeiffer, ER, Wright, AT, Edwards, AG, Stowe, JC, McNall, K, Tan, J, Niesman, I, Patel, HH, Roth, DM, Omens, JH & McCulloch, AD 2014, 'Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing', Journal of Molecular and Cellular Cardiology, vol. 76, pp. 265-274. https://doi.org/10.1016/j.yjmcc.2014.09.014
Pfeiffer, E. R. ; Wright, A. T. ; Edwards, A. G. ; Stowe, J. C. ; McNall, K. ; Tan, J. ; Niesman, I. ; Patel, H. H. ; Roth, D. M. ; Omens, J. H. ; McCulloch, A. D. / Caveolae in ventricular myocytes are required for stretch-dependent conduction slowing. In: Journal of Molecular and Cellular Cardiology. 2014 ; Vol. 76. pp. 265-274.
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AU - Tan, J.

AU - Niesman, I.

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