Ionic basis for excitability of normal rat kidney (NRK) fibroblasts

Ionic membrane conductances of normal rat kidney (NRK) fibroblasts were characterized by whole-cell voltage-clamp experiments on single cells and small cell clusters and their role in action potential firing in these cells and in monolayers was studied in current-clamp experiments. Activation of an L-type calcium conductance (G_CaL) is responsible for the initiation of an action potential, a calcium-activated chloride conductance (G_Cl(Ca)) determines the plateau phase of the action potential, and an inwardly rectifying potassium conductance (G_Kir) is important for the generation of a resting potential of approximately -70 mV and contributes to action potential depolarization and repolarization. The unique property of the excitability mechanism is that it not only includes voltage-activated conductances (G_CaL, G_Kir) but that the intracellular calcium dynamics is also an essential part of it (via G_Cl(Ca)). Excitability was found to be an intrinsic property of a fraction (∼25%) of the individual cells, and not necessarily dependent on gap junctional coupling of the cells in a monolayer. Electrical coupling of a patched cell to neighbor cells in a small cluster improved the excitability because all small clusters were excitable. Furthermore, cells coupled in a confluent monolayer produced broader action potentials. Thus, electrical coupling in NRK cells does not merely serve passive conduction of stereotyped action potentials, but also seems to play a role in shaping the action potential.