scholarly journals Regulation of Maximal Open Probability Is a Separable Function of Cavβ Subunit in L-type Ca2+ Channel, Dependent on NH2 Terminus of α1C (Cav1.2α)

2006 ◽  
Vol 128 (1) ◽  
pp. 15-36 ◽  
Author(s):  
Nataly Kanevsky ◽  
Nathan Dascal
Keyword(s):  
Initial Segment ◽  
Xenopus Oocytes ◽  
Surface Expression ◽  
Amino Acid Residues ◽  
Open Probability ◽  
Separable Function ◽  
Voltage Dependent ◽  
Cav1.2 Channels ◽  
Channel Dependent ◽  
Necessary And Sufficient

β subunits (Cavβ) increase macroscopic currents of voltage-dependent Ca2+ channels (VDCC) by increasing surface expression and modulating their gating, causing a leftward shift in conductance–voltage (G-V) curve and increasing the maximal open probability, Po,max. In L-type Cav1.2 channels, the Cavβ-induced increase in macroscopic current crucially depends on the initial segment of the cytosolic NH2 terminus (NT) of the Cav1.2α (α1C) subunit. This segment, which we term the “NT inhibitory (NTI) module,” potently inhibits long-NT (cardiac) isoform of α1C that features an initial segment of 46 amino acid residues (aa); removal of NTI module greatly increases macroscopic currents. It is not known whether an NTI module exists in the short-NT (smooth muscle/brain type) α1C isoform with a 16-aa initial segment. We addressed this question, and the molecular mechanism of NTI module action, by expressing subunits of Cav1.2 in Xenopus oocytes. NT deletions and chimeras identified aa 1–20 of the long-NT as necessary and sufficient to perform NTI module functions. Coexpression of β2b subunit reproducibly modulated function and surface expression of α1C, despite the presence of measurable amounts of an endogenous Cavβ in Xenopus oocytes. Coexpressed β2b increased surface expression of α1C approximately twofold (as demonstrated by two independent immunohistochemical methods), shifted the G-V curve by ∼14 mV, and increased Po,max 2.8–3.8-fold. Neither the surface expression of the channel without Cavβ nor β2b-induced increase in surface expression or the shift in G-V curve depended on the presence of the NTI module. In contrast, the increase in Po,max was completely absent in the short-NT isoform and in mutants of long-NT α1C lacking the NTI module. We conclude that regulation of Po,max is a discrete, separable function of Cavβ. In Cav1.2, this action of Cavβ depends on NT of α1C and is α1C isoform specific.

Separable function of platelet release reaction and clot retraction

1986 ◽  
Vol 140 (1) ◽  
pp. 329-334 ◽  
Author(s):  
Yutaka Yatomi ◽  
Masaaki Higashihara ◽  
Akira Tanabe ◽  
Tatsuya Ohashi ◽  
Kyoya Takahata ◽  
...  
Keyword(s):  
Clot Retraction ◽  
Release Reaction ◽  
Separable Function ◽  
Platelet Release
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