HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 20, 21461-21468, May 14, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/20/21461    most recent M401084200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ji, G. Articles by Kotlikoff, M. I. Search for Related Content PubMed PubMed Citation Articles by Ji, G. Articles by Kotlikoff, M. I. Social Bookmarking                      What's this?

Ca²⁺-sensing Transgenic Mice

POSTSYNAPTIC SIGNALING IN SMOOTH MUSCLE^*

Guangju Ji, Morris E. Feldman, Ke-Yu Deng, Kai Su Greene, Jason Wilson, Jane C. Lee, Robyn C. Johnston, Mark Rishniw, Yvonne Tallini, Jin Zhang, Winthrop G. Wier, Mordecai P. Blaustein, Hong-Bo Xin, Junichi Nakai¶, and Michael I. Kotlikoff||

From the Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, the Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, and the ^¶Laboratory for Neuronal Circuit Dynamics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan

Genetically encoded signaling proteins provide remarkable opportunities to design and target the expression of molecules that can be used to report critical cellular events in vivo, thereby markedly extending the scope and physiological relevance of studies of cell function. Here we report the development of a transgenic mouse expressing such a reporter and its use to examine postsynaptic signaling in smooth muscle. The circularly permutated, Ca²⁺-sensing molecule G-CaMP (Nakai, J., Ohkura, M., and Imoto, K. (2001) Nat. Biotechnol. 19, 137-141) was expressed in vascular and non-vascular smooth muscle and functioned as a lineage-specific intracellular Ca²⁺ reporter. Detrusor tissue from these mice was used to identify two separate types of postsynaptic Ca²⁺ signals, mediated by distinct neurotransmitters. Intrinsic nerve stimulation evoked rapid, whole-cell Ca²⁺ transients, or "Ca²⁺ flashes," and slowly propagating Ca²⁺ waves. We show that Ca²⁺ flashes occur through P2X receptor stimulation and ryanodine receptor-mediated Ca²⁺ release, whereas Ca²⁺ waves arise from muscarinic receptor stimulation and inositol trisphosphate-mediated Ca²⁺ release. The distinct ionotropic and metabotropic postsynaptic Ca²⁺ signals are related at the level of Ca²⁺ release. Importantly, individual myocytes are capable of both postsynaptic responses, and a transition between Ca²⁺-induced Ca²⁺ release and inositol trisphosphate waves occurs at higher synaptic inputs. Ca²⁺ signaling mice should provide significant advantages in the study of processive biological signaling.

Received for publication, January 30, 2004

^* This work was supported by National Institutes of Health Grants HL045239, D58795, and DK065992 (to M. I. K.), HL45215 (to M. P. B.), and HL64708 (to W. G. W.). 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.

^|| To whom correspondence should be addressed: Dept. of Biomedical Sciences, College of Veterinary Medicine, Cornell University, T4018 VRT, Box 11, Ithaca, NY 14853-6401. Tel.: 607-253-3336; Fax: 607-253-4447; E-mail: mik7{at}cornell.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H.-L. Ding, J. W. Ryder, J. T. Stull, and K. E. Kamm Signaling Processes for Initiating Smooth Muscle Contraction upon Neural Stimulation J. Biol. Chem., June 5, 2009; 284(23): 15541 - 15548. [Abstract] [Full Text] [PDF]

				J. He, L. Ma, S. Kim, J. Nakai, and C. R. Yu Encoding Gender and Individual Information in the Mouse Vomeronasal Organ Science, April 25, 2008; 320(5875): 535 - 538. [Abstract] [Full Text] [PDF]

				L. W. M. Nausch, J. Ledoux, A. D. Bonev, M. T. Nelson, and W. R. Dostmann Differential patterning of cGMP in vascular smooth muscle cells revealed by single GFP-linked biosensors PNAS, January 8, 2008; 105(1): 365 - 370. [Abstract] [Full Text] [PDF]

				J. Zacharia, J. Zhang, and W. G. Wier Ca2+ signaling in mouse mesenteric small arteries: myogenic tone and adrenergic vasoconstriction Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1523 - H1532. [Abstract] [Full Text] [PDF]

				M. I. Kotlikoff Genetically encoded Ca2+ indicators: using genetics and molecular design to understand complex physiology J. Physiol., January 1, 2007; 578(1): 55 - 67. [Abstract] [Full Text] [PDF]

				Y. N. Tallini, M. Ohkura, B.-R. Choi, G. Ji, K. Imoto, R. Doran, J. Lee, P. Plan, J. Wilson, H.-B. Xin, et al. Imaging cellular signals in the heart in vivo: Cardiac expression of the high-signal Ca2+ indicator GCaMP2 PNAS, March 21, 2006; 103(12): 4753 - 4758. [Abstract] [Full Text] [PDF]

				G. Ji, M. Feldman, R. Doran, W. Zipfel, and M. I. Kotlikoff Ca2+-Induced Ca2+ Release through Localized Ca2+ Uncaging in Smooth Muscle J. Gen. Physiol., February 27, 2006; 127(3): 225 - 235. [Abstract] [Full Text] [PDF]

				M. I. Kotlikoff and N. Y. Tallini Imaging Dynamic Cellular Events in the Lung J. Gen. Physiol., May 31, 2005; 125(6): 529 - 530. [Full Text] [PDF]

				T. A. Pologruto, R. Yasuda, and K. Svoboda Monitoring Neural Activity and [Ca2+] with Genetically Encoded Ca2+ Indicators J. Neurosci., October 27, 2004; 24(43): 9572 - 9579. [Abstract] [Full Text] [PDF]