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J. Biol. Chem., Vol. 278, Issue 23, 20860-20864, June 6, 2003

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Long Distance Communication between Muscarinic Receptors and Ca²⁺ Release Channels Revealed by Carbachol Uncaging in Cell-attached Patch Pipette^*

Michael C. Ashby  , Cristina Camello-Almaraz ¶, Oleg V. Gerasimenko, Ole H. Petersen and Alexei V. Tepikin 

From the Medical Research Council Secretory Control Research Group, The Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, United Kingdom

We have investigated the characteristics of cytosolic Ca²⁺ signals induced by muscarinic receptor activation of pancreatic acinar cells that reside within intact pancreatic tissue. We show that these cells exhibit global Ca²⁺ waves and local apical Ca²⁺ spikes. This is the first evidence for local Ca²⁺ signaling in undissociated pancreatic tissue. The mechanism of formation of localized Ca²⁺ signals was examined using a novel approach involving photolysis of caged carbachol inside a patch pipette attached to the basal surface of an acinar unit. This local activation of basal muscarinic receptors elicited local cytosolic Ca²⁺ spikes in the apical pole more than 15 µm away from the site of stimulation. In some experiments, local basal receptor activation elicited a Ca²⁺ wave that started in the apical pole and then spread toward the base. Currently, there are two competing hypotheses for preferential apical Ca²⁺ signaling. One invokes the need for structural proximity of the cholinergic receptors and the Ca²⁺ release channels in the apical pole, whereas the other postulates long distance communication between basal receptors and the channels. Our intrapipette uncaging experiments provide definitive evidence for long distance communication between basal muscarinic receptors and apical Ca²⁺ release channels.

Received for publication, March 13, 2003

^* This work was supported by a Medical Research Council program grant (to O. H. P. and A. V. T.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Present address: Dept. of Anatomy, Medical Research Council Centre for Synaptic Plasticity, University of Bristol, Medical School, University Walk, Bristol BS8 1TD, United Kingdom.

Supported by a Wellcome Trust Prize Studentship. To whom correspondence may be addressed. E-mail: M.C.Ashby{at}bristol.ac.uk (M. C. A.) or a.tepikin{at}liv.ac.uk (A. V. T.).

^¶ Present address: Dept. of Physiology, Faculty of Veterinary Science, P. O. Box 643, 10071 Caceres, Spain.

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