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