Abstract:
:When we are frightened, our hearts beat more rapidly and forcefully so we can fight more intensely or run away faster. This fight-or-flight response is triggered by the release of norepinephrine from neurons of the sympathetic nervous system. Norepinephrine activates the classic β-adrenergic receptor-heterotrimeric G(s) protein-adenylyl cyclase-adenosine 3',5'-monophosphate-protein kinase A (PKA) signaling cascade. One of the main PKA targets implicated in this response is the L-type Ca2+ channel Ca(V)1.2, which mediates Ca2+ influx into cardiomyocytes. Because of its central function in regulating heartbeat, and because the underlying molecular mechanism has remained elusive, understanding the regulation of Ca(V)1.2 has been considered the holy grail for the field of channel regulation. New evidence from the quest to solve the mystery of Ca(V)1.2 regulation has revealed that reproducible reconstitution of this regulation in heterologous cells requires a perfect balance of the ratio of Ca(V)1.2 to A-kinase anchor proteins (AKAPs). Proteolytic processing of the cytosolic C terminus of the central, pore-forming α₁1.2 subunit of Ca(V)1.2 contributed to its regulation by PKA, and Ser(1700) in the C terminus of the α₁1.2 subunit emerged as the relevant PKA phosphorylation site.
journal_name
Sci Signaljournal_title
Science signalingauthors
Hell JWdoi
10.1126/scisignal.3141pe33subject
Has Abstractpub_date
2010-09-28 00:00:00pages
pe33issue
141eissn
1945-0877issn
1937-9145pii
3/141/pe33journal_volume
3pub_type
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