Functional coupling of calcineurin and protein kinase A in mouse ventricular myocytes

Luis Fernando Santana, E. G. Chase, V. S. Votaw, Mark T. Nelson, R. Greven

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


We examined the role of the Ca2+-regulated protein phosphatase calcineurin in controlling Ca2+ signalling in mouse ventricular myocytes. Membrane currents and voltage were measured in single myocytes using the patch-clamp technique. Cytoplasmic Ca2+ concentration ([Ca2+] i) was measured in cells loaded with the fluorescent Ca2+ indicators fluo-4 or fura-2 using a confocal or epifluorescence microscope. Inhibition of calcineurin with cyclosporin A (CsA, 100 nM) or the calcineurin auto-inhibitory peptide (CiP, 100 μM), increased the amplitude and rate of decay of the evoked [Ca2+]i transient and also prolonged the action potential (AP) of ventricular myocytes to a similar extent. The effects of CsA (100 nM) and 100 μM CiP on the [Ca2+]i transient and AP were not additive. Calcineurin inhibition did not modify the K+ currents responsible for repolarisation of the mouse ventricle. Instead, inhibition of calcineurin increased the amplitude of the Ca2+ current (Ica) and the evoked calcium transient normalized to the Ica. Calcium sparks, which underlie the [Ca2+]i transient, had a higher frequency and amplitude, suggesting an elevation of SR calcium load. Inhibition of protein kinase A (PKA) prevented the effects of calcineurin inhibition, indicating that calcineurin opposes the actions of PKA. Finally, immunofluorescence images suggest that calcineurin and PKA co-localize near the T-tubules of ventricular myocytes. We propose that calcineurin and PKA are co-localized to control Ca2+ influx through calcium channels and calcium release through ryanodine receptors.

Original languageEnglish (US)
Pages (from-to)57-69
Number of pages13
JournalJournal of Physiology
Issue number1
StatePublished - Oct 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Physiology


Dive into the research topics of 'Functional coupling of calcineurin and protein kinase A in mouse ventricular myocytes'. Together they form a unique fingerprint.

Cite this