Synchronized Ca2+ signaling by intercellular propagation of Ca2+ action potentials in NRK fibroblasts.
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 electronically propagating action potentials travel intercellularly over long distances in an all-or-none fashion at a speed of approximately 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.
De Roos
A
A
Department of Cell Biology, University of Nijmegen, The Netherlands.
Willems
P H
PH
van Zoelen
E J
EJ
Theuvenet
A P
AP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020746:Calcium Channels, L-Type; D002460:Cell Line; D002712:Chlorides / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D007668:Kidney; D007700:Kinetics; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013324:Strontium / Q000378:metabolism; D013997:Time Factors
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D002712:Chlorides; D004533:Egtazic Acid; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D011188:Potassium; D001920:Bradykinin; D002118:Calcium; D013324:Strontium