====== David Friel, Ph.D. ====== #template(faculty_profile.php|... * FName: David * LName: Friel * Degree: Ph.D. * Picture: friel.jpg * Width: 310 * Position: Associate Professor * Department: Department of Neurosciences * Organization: Case Western Reserve University * Address_1: School of Medicine * Address_2: 10900 Euclid Ave * Address_3: Cleveland OH, 44106-4975 * Phone: (216) 368-4930 * Fax: (216) 368-4650 * Email: ddf2@case.edu * PubMed_Search: Friel DD + Case Western )# ===== RESEARCH INTERESTS ===== My main research interest is calcium signaling. Ionized free calcium (Ca2+) is important in regulating diverse cellular functions and serves as the critical link between a variety of physiological stimuli and their intracellular effectors. Specialized functions of Ca2+ in the nervous system include control of neurotransmitter release, membrane excitability and gene expression. Since Ca2+ produces many of its intracellular effects by interacting with Ca2+ binding proteins according to bimolecular reaction kinetics, the ultimate effect of Ca2+ entry (e.g. through voltage-gated Ca2+ channels in the plasma membrane that open in response to membrane depolarization during an action potential or synaptic transmission) depends on the dynamics of the intracellular free Ca2+ concentration [Ca2+]. One of the main goals of my research is to understand the determinants of [Ca2+] dynamics and their modulation. This is interesting, and challenging, given the presence of intracellular compartments, such as mitochondria and the endoplasmic reticulum, that are endowed with specialized Ca2+ transport systems that permit them to either accumulate or release Ca2+ in a highly regulated manner. Understanding Ca2+ signaling thus requires information about the changes in [Ca2+]i that occur within these compartments during stimulation and the specialized Ca2+ transport pathways (channels, pumps and exchangers) that are responsible for these changes. To obtain this information, a number of complementary experimental methods are employed, including the patch clamp technique to monitor Ca2+ movements across the plasma membrane under voltage-clamp, and variety of fluorescent Ca2+ indicators to monitor [Ca2+]i within different intracellular compartments and the spatial heterogeneity of [Ca2+]i within individual compartments as they occur during and after stimulation. Another focus of our research is to understand how Ca2+ regulatory dysfunction contributes to disease. We are currently studying how mutations in voltage-sensitive Ca2+ channels (VSCCs) lead to neurodegeneration, using mouse cerebellar Purkinje neurons as a model system. Previous studies have shown that mutations in P/Q-type VSCCs lead to Purkinje cell loss, but the mechanism linking the Ca2+ channel defect to cell death is unknown. Mutations in the same channel subtype are responsible for several forms of inherited diseases in humans (e.g. familial hemiplegic migraine, episodic ataxia type-2, and spinocerebellar ataxia type 6) so the results of our studies are expected to contribute to an understanding of how Ca2+ regulatory dysfunction contributes to human genetic disease. ===== SELECTED PUBLICATIONS ===== #template?key=Friel(dokudata.php|... * ID: 18669535 * Author: Liu S, Friel DD. * Volume: 129 * Issue: 1 * Year: 2008 * Date: 2008 Aug 14 * Journal: J Physiol * Pages: 93-103 [Epub ahead of print] * Title: Impact of the leaner P/Q-type Ca2+ channel mutation on excitatory synaptic transmission in cerebellar Purkinje cells * Selected: true ---- * ID: 18093175 * Author: Ovsepian SV, Friel DD. * Volume: 27 * Issue: 1 * Year: 2008 * Date: 2007 Dec 17 * Journal: Eur J Neurosci * Pages: 93-103 * Title: The leaner P/Q-type calcium channel mutation renders cerebellar Purkinje neurons hyper-excitable and eliminates Ca2+-Na+ spike bursts. * Selected: true ---- * ID: 18054801 * Author: Friel DD, Chiel HJ. * Volume: 31 * Issue: 1 * Year: 2008 * Date: 2007 Dec 4 * Journal: Trends Neurosci * Pages: 8-19 * Review: true * Title: Calcium dynamics: analyzing the Ca2+ regulatory network in intact cells. * Selected: true ---- * ID: 17190902 * Author: Patterson M, Sneyd J, Friel DD. * Volume: 129 * Issue: 1 * Year: 2007 * Date: 2007 Jan 1 * Journal: J Gen Physiol * Pages: 29-56 * Title: Depolarization-induced calcium responses in sympathetic neurons: relative contributions from Ca2+ entry, extrusion, ER/mitochondrial Ca2+ uptake and release, and Ca2+ buffering. * Selected: true * Abstract: [[http://www.jgp.org/cgi/content/abstract/129/1/29|Abstract]] * Full: [[http://www.jgp.org/cgi/content/full/129/1/29|Full]] * PDF: [[http://www.jgp.org/cgi/reprint/129/1/29|PDF]] ---- * ID: 16415055 * Author: Jones SW, Friel DD. * Volume: 90 * Issue: 5 * Year: 2006 * Date: 2006 Mar 1 * Journal: Biophys J * Pages: L39-L41 * Title: The amplitude distribution of release events through a fusion pore. * Selected: true * Abstract: [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16415055&query_hl=3&itool=pubmed_DocSum|Abstract]] * Full: [[http://www.biophysj.org/cgi/content/full/90/5/L39|Full]] * PDF: [[http://www.biophysj.org/cgi/reprint/90/5/L39|PDF]] ---- * Author: Friel, DD. * Year: 2003 * Title: Mitochondrial and ER-calcium uptake and release fluxes and their interplay in intact nerve cells. In: Understanding Calcium Dynamics, Lecture Notes in Physics. Eds. M. Falcke, H. Malchow. Springer, Berlin. * Volume: 623 * Pages: 37-65 * Review: true * PDF: {{friel_lnp_rev_v623.pdf|PDF}} ---- * ID: 11865019 * Author: Albrecht MA, Colegrove SL, Friel DD. * Volume: 119 * Issue: 3 * Year: 2002 * Date: 2002 Mar * Journal: J Gen Physiol * Pages: 211-233 * Title: Differential regulation of ER Ca2+ uptake and release rates accounts for multiple modes of Ca2+-induced Ca2+ release. * Selected: true * Abstract: [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11865019&query_hl=3&itool=pubmed_DocSum|Abstract]] * Full: [[http://www.jgp.org/cgi/content/full/119/3/211|Full]] * PDF: [[http://www.jgp.org/cgi/reprint/119/3/211|PDF]] ---- * ID: 11429446 * Author: Albrecht MA, Colegrove SL, Hongpaisan J, Pivovarova NB, Andrews SB, Friel DD. * Volume: 118 * Issue: 1 * Year: 2001 * Date: 2001 Jul * Journal: J Gen Physiol * Pages: 83-100 * Title: Multiple modes of calcium-induced calcium release in sympathetic neurons I: attenuation of endoplasmic reticulum Ca2+ accumulation at low [Ca2+]i during weak depolarization. * Selected: true * Abstract: [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11429446&query_hl=12&itool=pubmed_docsum|Abstract]] * Full: [[http://www.jgp.org/cgi/content/full/118/1/83|Full]] * PDF: [[http://www.jgp.org/cgi/reprint/118/1/83|PDF]] ---- * ID: 11429447 * Author: Hongpaisan J, Pivovarova NB, Colegrove SL, Leapman RD, Friel DD, Andrews SB. * Volume: 118 * Issue: 1 * Year: 2001 * Date: 2001 Jul * Journal: J Gen Physiol * Pages: 101-112 * Title: Multiple modes of calcium-induced calcium release in sympathetic neurons II: a [Ca2+](i)- and location-dependent transition from endoplasmic reticulum Ca accumulation to net Ca release. * Selected: true * Abstract: [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11429447&query_hl=12&itool=pubmed_docsum|Abstract]] * Full: [[http://www.jgp.org/cgi/content/full/118/1/101|Full]] * PDF: [[http://www.jgp.org/cgi/reprint/118/1/101|PDF]] ---- * ID: 11115370 * Author: Friel DD. * Volume: 28 * Issue: 5-6 * Year: 2000 * Date: 2000 Nov-Dec * Journal: Cell Calcium * Pages: 307-316 * Review: true * Title: Mitochondria as regulators of stimulus-evoked calcium signals in neurons. ---- * ID: 10694264 * Author: Colegrove SL, Albrecht MA, Friel DD. * Volume: 115 * Issue: 3 * Year: 2000 * Date: 2000 Mar * Journal: J Gen Physiol * Pages: 371-388 * Title: Quantitative analysis of mitochondrial Ca2+ uptake and release pathways in sympathetic neurons. Reconstruction of the recovery after depolarization-evoked [Ca2+]i elevations. * Selected: true ---- * ID: 10694263 * Author: Colegrove SL, Albrecht MA, Friel DD. * Volume: 115 * Issue: 3 * Year: 2000 * Date: 2000 Mar * Journal: J Gen Physiol * Pages: 351-370 * Title: Dissection of mitochondrial Ca2+ uptake and release fluxes in situ after depolarization-evoked [Ca2+](i) elevations in sympathetic neurons. * Selected: true ---- * ID: 10414966 * Author: Pivovarova NB, Hongpaisan J, Andrews SB, Friel DD. * Volume: 19 * Issue: 15 * Year: 1999 * Date: 1999 Aug 1 * Journal: J Neurosci * Pages: 6372-84 * Title: Depolarization-induced mitochondrial Ca accumulation in sympathetic neurons: spatial and temporal characteristics. * Selected: true ---- * ID: 8646769 * Author: Friel DD. * Volume: 85 * Issue: 5 * Year: 1996 * Date: 1996 May 31 * Journal: Cell * Pages: 617-619 * Review: true * Title: TRP: its role in phototransduction and store-operated Ca2+ entry. ---- * ID: 7612818 * Author: Friel DD. * Volume: 68 * Issue: 5 * Year: 1995 * Date: 1995 May * Journal: Biophys J * Pages: 1752-1766 * Title: [Ca2+]i oscillations in sympathetic neurons: an experimental test of a theoretical model. * Selected: true ---- * Author: Friel, DD. * Year: 1995 * Title: [Ca2+]i Oscillations in neurons. In: Ciba Symposium No. 188: [Ca2+]i waves, gradients and oscillations. Wiley, Chichester. * Review: true * Abstract: [[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7587619&dopt=Abstract|Abstract]] )# #template?query=Selected&key=Friel(publications.php|...)# ===== REVIEWS ===== #template?query=Review&key=Friel(publications.php|...)# #template?key=Friel(dokudata.php|...)# ~~NOTOC~~