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Am J Physiol Cell Physiol 273: C1900-C1907, 1997;
0363-6143/97 $5.00
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Vol. 273, Issue 6, C1900-C1907, December 1997

Synchronized Ca2+ signaling by intercellular propagation of Ca2+ action potentials in NRK fibroblasts

Albert D. G. De Roos1, Peter H. G. M. Willems2, Everardus J. J. Van Zoelen1, and Alexander P. R. Theuvenet1

Departments of 1 Cell Biology and 2 Biochemistry, University of Nijmegen, 6525 ED Nijmegen, The Netherlands

The intercellular propagation of Ca2+ waves by diffusion of inositol trisphosphate has been shown to be a general mechanism by which nonexcitable cells communicate. Here, we show that monolayers of normal rat kidney (NRK) fibroblasts behave like a typical excitable tissue. In confluent monolayers of these cells, Ca2+ action potentials can be generated by local depolarization of the monolayer on treatment with either bradykinin or an elevation of the extracellular K+ concentration. These electrotonically propagating action potentials travel intercellularly over long distances in an all-or-none fashion at a speed of ~6.1 mm/s and can be blocked by L-type Ca2+ channel blockers. The action potentials are generated by depolarizations beyond the threshold value for L-type Ca2+ channels of about -15 mV. The result of these locally induced, propagating Ca2+ action potentials is an almost synchronous, transient increase in the intracellular Ca2+ concentration in large numbers of cells. These data show that electrically coupled fibroblasts can form an excitable syncytium, and they elucidate a novel mechanism of intercellular Ca2+ signaling in these cells that may coordinate synchronized multicellular responses to local stimuli.

bradykinin; intracellular calcium; calcium channels; normal rat kidney fibroblasts


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