Department of Physiology and Cell Biiology

 

 

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Kathleen Keef, Ph. D.

Professor


Since my arrival at the University of Nevada, Reno in 1987 my work has focused primarily upon the ionic mechanisms underlying the control of smooth muscle contraction. This work has included studies of both vascular and visceral smooth muscles. We have studied a variety of different pathways which regulate smooth muscle contraction including the actions of autonomic and enteric nerves and their associated post-junctional receptors, pacemaker activity and stretch dependent myogenic responses. To investigate these pathways a number of different approaches are used. At the whole tissue level both contractile and electrical activity are measured using strain gauges and intracellular microelectrode techniques. These results are then used to direct more mechanistic studies of the underlying ionic conductances using whole-cell and isolated patch recording techniques on isolated smooth muscle myocytes. Immunohistochemical techniques have also been used to determine the spatial localization of relevant proteins. In recent years this work has been extended to include studies directed toward identifying unique splice variants of channels that are present in tissues. In some cases channels have been cloned and expressed in heterologous expression systems to identify their biophysical characteristics and to further explore the molecular mechanisms underlying regulation of the channel.

 

Search For Dr. Keef's Publications In PubMed


Selected Publications

Fukao, M., Mason, H.S., Kenyon, J.L., Horowitz, B and Keef, K.D. Regulation of BKCa channels expressed in HEK293 cells by epoxyeicosatrienoic acid. Mol. Pharmacol. 59: 16-23, 2001.

Zhong, J. Hume, J.R. and Keef, K.D. ß-adrenergic stimulation of vascular L-type Ca2+ channels involves both G-protein as and ß subunits. J. Physiol. 531: 105-115, 2001.

Mutafova-Yambolieva, V.N. and Keef, K.D. Frequency dependent a2-adrenoceptor mediated modulation of excitatory junction potentials in guinea-pig mesenteric artery. Eur. J. Pharmacol., 411: 123-127, 2001.

Keef, K.D., Hume, JR and Zhong, J. Regulation of cardiac and smooth muscle Ca2+ channels (CaV1.2a,b) by protein kinases. Invited Review, Am.J.Physiol. 281: C1743-C1756, 2001.

Keef, K.D., Anderson, U., O’Driscoll, K., Ward, S.M. and Sanders, K.M.. Electrical activity induced by nitric oxide In canine colonic circular muscle. Am. J. Physiol. 282: G123-G129, 2002.

Ward, S. M., Gershon, M. D., Bayguinov, J. R., Nelson, C., Keef, K.D. and Sanders,K.M. Distribution of ICC and electrical activity in ganglionic and aganglionic colons of mice. Am. J. Physiol. 283: G445-G456, 2002.

Tichenor, S.D., I. L.O. Buxton, P. Johnson, K. O’Driscoll, and Keef, K.D. Excitatory motor innervation in the canine rectoanal region: role of changing receptor populations. Br.J.Pharmacol. 137: 1321-9, 2002.

Horiguchi, K., Keef, K.D. and Ward, S.M. Distribution of interstitial cells of Cajal in the tunica muscularis of the canine rectoanal region. Am. J. Physiol. 284(5):G756-67, 2003.

Mutafova-Yambolieva, V.N., O’Driscoll, K., Farrelly, A., Ward, S.M. and Keef, K.D. Spatial localization and properties of pacemaker potentials in the canine rectoanal region. Am. J. Physiol. 284(5):G748-55, 2003.

Farrelly, A.M., S. Ro, B. Callaghan, N. Fleming, B. Horowitz, K.M. Sanders and K.D. Keef. Expression and function of KCNH2 (HERG) in the human jejunum. Am. J. Physiol., 284(6):G883-95, 2003.

Callaghan, B., Koh, S.D. and Keef, K.D. Muscarinic M2 receptor stimulation of Cav1.2b requires PI3K, PKC and c-Src. Circ. Res. 94(5):626-333, 2004.

Lee H.K., Ro S, Keef K.D., Kim Y.H., Kim H.W., Horowitz B, Sanders K.M. Differential expression of P2X-purinoceptor subtypes in circular and longitudinal muscle of canine colon. Neurogastroenterol Motil. 17(4):575-84, 2005.

Callaghan B, Zhong J, Keef KD. Signaling pathway underlying stimulation of L-type Ca2+ channels in rabbit portal vein myocytes by recombinant Gbetagamma subunits. Am J Physiol Heart Circ Physiol 291:H2541-2546 (2006)

Ro S, Kang SH, Farrelly AM, Ordog T, Partain R, Fleming N, Sanders KM,
Kenyon JL, Keef KD. Template switching within exons 3 and 4 of KV11.1 (HERG) gives rise to a 5' truncated cDNA. Biochem Biophys Res Commun 345:1342-1349 (2006)

Cobine CA, Callaghan BP, Keef KD. Role of L-type Calcium Channels and PKC in Active Tone Development in Rabbit Coronary Artery. Am J Physiol Heart Circ Physiol. Epub ahead of print: Feb 2 (2007)

In my spare time I also enjoy activities such as hiking in the Sierra Nevada (see below).

View of Lake Tahoe from the top of Mt. Rose