Auxiliary β Subunits differentially determine pka utilization of distinct regulatory sites on Cav1.3 L type Ca2+ channels

Yixin Liang, Steven Tavalin

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

L-type calcium channels (Cav1.1-Cav1.4) link Ca2+ influx to membrane depolarization and serve a critical role in regulating membrane excitability, muscle contraction, hormone secretion, and gene transcription. In many tissues, L-type calcium channel activity (Cav1.1 and Cav1.2) is enhanced by transmitters and hormones that activate the cAMP-dependent protein kinase (PKA), which is largely thought to be mediated via phosphorylation of the pore forming a subunit. However, the ability of PKA to regulate Cav1.3 and the sites contributing to effective modulation of channel activity remains to be established. Using HEK 293 cells, we demonstrate that currents carried by the long C-terminal splice variant of Cav1.3 (Cav1.3L) are selectively enhanced compared to the short C-terminal splice variant (Cav1.3S) when the catalytic subunit of PKA is introduced into the cell via the whole-cell recording electrode. However, the persistence of this regulation is dependent on the identity of the auxiliary b subunit, such that PKA produces only a transient increase in the presence of b3 while a persistent increase is observed in the presence of the b2a subunit. Site-directed mutagenesis of consensus PKA phosphorylation sites revealed that Ser1964 and Ser1743 in Cav1.3L were the predominant sites controlling PKA modulation in the presence of the b3 and b2a auxiliary subunits, respectively. Therefore, b subunits determine the contribution of distinct sites within Cav1.3 towards PKA-mediated enhancement of channel activity. These data suggest that auxiliary b subunits govern the access of signaling enzymes to L-type calcium channels.

Original languageEnglish (US)
Pages (from-to)102-112
Number of pages11
JournalChannels
Volume1
Issue number2
DOIs
StatePublished - Jan 1 2007

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Protein Kinases
L-Type Calcium Channels
Phosphorylation
Modulation
Hormones
Membranes
Mutagenesis
HEK293 Cells
Depolarization
Patch-Clamp Techniques
Transcription
Muscle Contraction
Site-Directed Mutagenesis
Cyclic AMP-Dependent Protein Kinases
Muscle
Transmitters
Catalytic Domain
Electrodes
Genes
Tissue

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry

Cite this

Auxiliary β Subunits differentially determine pka utilization of distinct regulatory sites on Cav1.3 L type Ca2+ channels. / Liang, Yixin; Tavalin, Steven.

In: Channels, Vol. 1, No. 2, 01.01.2007, p. 102-112.

Research output: Contribution to journalArticle

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