Premium
Potentiation of L‐Type Calcium Current (Cav1.2) by Intracellular Positive Pressure: Role of the Cav1.2 C‐terminus
Author(s) -
Gui Peichun,
Zamponi G W,
Davis G E,
Davis M J
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a538
Subject(s) - cav1.2 , mechanosensitive channels , chemistry , microbiology and biotechnology , intracellular , calcium in biology , biophysics , mechanotransduction , long term potentiation , integrin , patch clamp , voltage dependent calcium channel , calcium channel , calcium , biochemistry , biology , ion channel , cell , receptor , organic chemistry
The myogenic response is the rapid and maintained constriction of a blood vessel in response to pressure elevation. A role for integrins in this mechanotransduction process has been suggested. Recent studies in our lab indicate that L‐type calcium current is potentiated by activation of α5β1 integrin for both native and heterologously expressed channels, requiring PKA‐ and Src‐ phosphorylation of Cav1.2 C‐terminal residues. To test whether Cav1.2 channels are intrinsically mechanosensitive, patch clamp methods were used to investigate the properties of Cav1.2 expressed in HEK 293 cells during intracellular application of positive pressure to expand the plasma membrane. In cells expressing the pore‐forming smooth muscle isoform (Cav1.2b) alone or Cav1.2b plus β2a/α2δ‐1 accessory subunits, positive pipette pressures of 10~30 mmHg resulted in 20~45% increases in peak inward barium current, which was substantially less than the potentiation by α5β1 integrin activation (95%). Similar results were found for the neuronal L‐type channel isoform Cav1.2c (+/−β1b/α2δ). Neither intracellular application of PKA inhibitor peptide nor mutagenesis of the PKA phosphorylation site on Cav1.2 at Ser 1901 blocked the effect of positive pressure. Our results suggest that the Cav1.2 calcium channel subunit is intrinsically mechanosensitive and that enhanced channel activity in response to intracellular positive pressure may not involve the integrin‐extracellular matrix axis.