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¹ Department of Physiology, Martin Luther University, 06097 Halle, Germany

As integrins are thought to function as mechanoreceptors, we studied whether they could mediate mechanical modulation of the L-type Ca²⁺ channel current (I_Ca) in guinea-pig cardiac ventricular myocytes (CVMs). CVMs were voltage clamped with 280 ms pulses from –45 to 0 mV at 0.5 Hz (1.8 mM [Ca²⁺]_o, 22°C). Five minutes after whole-cell access (designated as 0 min) peak I_Ca was determined from a current–voltage (I–V) curve. Additional recordings were made after 5, 10 and 15 min. At control, I_Ca was not stable, but ran down during these periods. This run-down of I_Ca was attenuated by soluble fibronectin (FN) and was changed to an enhancement of I_Ca 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 I_Ca; however, I_Ca 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 I_Ca in stimulated CVMs. Augmentation of I_Ca 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 I_Ca 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 I_Ca 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.

(Received 5 July 2004; accepted after revision 3 August 2005; first published online 5 August 2004)
Corresponding author U. Rueckschloss: Department of Physiology, Martin Luther University, 06097 Halle, Germany. Email: uwe.rueckschloss{at}medizin.uni-halle.de

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