The Journal of Neurophysiology Vol. 86 No. 4 October 2001, pp. 1826-1838
Copyright ©2001 by the American Physiological Society

Indirectly Gated Cl-Dependent Cl Channels Sense Physiological Changes of Extracellular Chloride in the Leech

 ¹Fakultät für Biologie, Universität Konstanz, D-78457 Konstanz, Germany;  ²Stazione Zoologica "Anton Dohrn," I-80121 Naples, Italy; and  ³Department of Biology, Emory University, Atlanta, Georgia 30322

Wenning, Angela, Christian F. J. Erxleben, and Ronald L. Calabrese. Indirectly Gated Cl-Dependent Cl Channels Sense Physiological Changes of Extracellular Chloride in the Leech. J. Neurophysiol. 86: 1826-1838, 2001. The maintenance of ion homeostasis requires adequate ion sensors. In leeches, 34 nephridial nerve cells (NNCs) monitor the Cl concentration of the blood. After a blood meal, the Cl concentration of leech blood triples and is gradually restored to its normal value within 48 h after feeding. As previously shown in voltage-clamp experiments, the Cl sensitivity of the NNCs relies on a persistent depolarizing Cl current that is turned off by an increase of the extracellular Cl concentration. The activation of this Cl-dependent Cl current is independent of voltage and of extra- and intracellular Ca²⁺. The transduction mechanism is now characterized on the single-channel level. The NNC's sensitivity to Cl is mediated by a slowly gating Cl-dependent Cl channel with a mean conductance of 50 pS in the cell-attached configuration. Gating of the Cl channel is independent of voltage, and channel activity is independent of extra- and intracellular Ca²⁺. Channel activity and the macroscopic current are reversibly blocked by bumetanide. In outside-out patches, changes of the extracellular Cl concentration do not affect channel activity, indicating that channel gating is not via direct interaction of extracellular Cl with the channel. As shown by recordings in the cell-attached configuration, the activity of the channels under the patch is instead governed by the Cl concentration sensed by the rest of the cell. We postulate a membrane-bound Cl-sensing receptor, whichon the increase of the extracellular Cl concentrationcloses the Cl channel via a yet unidentified signaling pathway.