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Discrete Microdomains with High Concentration of cAMP in Stimulated Rat Neonatal Cardiac Myocytes
Manuela Zaccolo,*Tullio Pozzan
The second messenger cyclic adenosine monophosphate (cAMP) is
the most important modulator of sympathetic control over cardiaccontractility. In cardiac myocytes and many other cell types,however,
cAMP transduces the signal generated upon stimulationof various
receptors and activates different cellular functions,raising the issue
of how specificity can be achieved. In the generalfield of signal
transduction, the view is emerging that specificityis guaranteed by
tight localization of signaling events. Here,we show that in neonatal
rat cardiac myocytes, -adrenergic stimulationgenerates multiple
microdomains with increased concentration ofcAMP in correspondence
with the region of the transverse tubule/junctionalsarcoplasmic
reticulum membrane. The restricted pools of cAMPshow a range of action
as small as approximately 1 micrometer,and free diffusion of the
second messenger is limited by the activityof phosphodiesterases.
Furthermore, we demonstrate that such gradientsof cAMP specifically
activate a subset of protein kinase A moleculesanchored in proximity
to the T tubule.
Department of Biomedical Sciences and Venetian Institute for
Molecular Medicine, University of Padua, Via Orus 2, 35129 Padua,
Italy.
*
To whom correspondence should be addressed. E-mail:
manuela.zaccolo{at}unipd.it
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-adrenergic stimulation generates multiple
microdomains with increased concentration of cAMP in correspondence
with the region of the transverse tubule/junctional sarcoplasmic
reticulum membrane. The restricted pools of cAMP show a range of action
as small as approximately 1 micrometer, and free diffusion of the
second messenger is limited by the activity of phosphodiesterases.
Furthermore, we demonstrate that such gradients of cAMP specifically
activate a subset of protein kinase A molecules anchored in proximity
to the T tubule.
