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- Title
Contraction augments L-type Ca<sup>2+</sup> currents in adherent guinea-pig cardiomyocytes.
- Authors
Rueckschloss, Uwe; Isenberg, Gerrit
- Abstract
As integrins are thought to function as mechanoreceptors, we studied whether they could mediate mechanical modulation of the L-type Ca2+ channel current (Ica) in guinea-pig cardiac ventricular myocytes (CVMs). CVMs were voltage clamped with 280 ms pulses from--45 to 0 m V at 0.5 Hz (1.8 mM [Ca2+]o, 22°C). Five minutes after whole-cell access (designated as 0 min) peak ICa was determined from a current-voltage (I-V) curve. Additional recordings were made after 5, 10 and 15 min. At control, ICaa was not stable, but ran down during these periods. This run-down of ICa was attenuated by soluble fibronectin (FN) and was changed to an enhancement of ICa when CVMs were attached to FN-coated coverslips. Soluble peptide containing the integrin binding sequence of FN, Arg-Gly-Asp (RGD motif), did not modulate ICa; however, ICa increased in stimulated CVMs attached to RGD peptide-coated coverslips. The effect was not specific to integrins, because attachment to poly-D-lysine-coated coverslips also augmented ICa in stimulated CVMs. Augmentation of ICa by immobilized FN required rhythmical contraction of attached CVMs, because it was attenuated without electrical stimulation and after cell dialysis with the calcium chelator BAPTA. Furthermore, contraction-induced augmentation of ICa in FN-attached CVMs was sensitive to inhibition of protein kinase C (PKC; by Ro-31-8220), inhibition of tyrosine kinase activity (herbimycin A) and cytoskeletal depolymerization (cytochalasin D or colchicine). We attribute augmentation of ICa to the activation of signalling cascades by shear forces that are generated when CVMs contract against attachment; in vivo similar signals may occur when CVMs contract against attachment of integrins to the extracellular matrix.
- Subjects
INTEGRINS; MECHANORECEPTORS; HEART cells; MUSCLE cells; FIBRONECTINS; GUINEA pigs
- Publication
Journal of Physiology, 2004, Vol 560, Issue 2, p403
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2004.062604