Rocky Mountains!
Cast & Stage
 
 
 
 

Mircea C. Iftinca   Postdoctorate Fellow    
MD University of Medicine and Pharmacy, Bucharest
PhD University of Calgary 2004

Current Gig:
Clinical Resident
Royal Columbian Hospital
University of British Columbia
Vancouver British Columbia Canada

Phone: (403) 615-4625 (cell)
iftinca@interchange.ubc.ca

Training
1991
Doctor of Medicine
University of Medicine and Pharmacy
Bucharest Romania

2004
PhD Cardio-Respiratory Science
University of Calgary
Calgary Alberta
Supervisor: Dr. W.C. Cole

2004 - 2008
Postdoctorate
University of Calgary
Calgary Alberta
Supervisors: R.W. Turner, G. Zamponi
Awards
PhD
CIHR Doctoral Studentship

PDF
AHFMR Postdoctoral Fellowship 2007
Research Focus: Kinetics and function of T-type calcium channel subtypes
Approach: Electrophysiology in vitro, pharmacology, molecular biology
Preparations: Expression systems, in vitro slice preparations
Below are short summaries of my publications.

PhD Thesis research:
My PhD work centered on endothelium-dependent and -independent relaxation mechanisms in rat basilar artery after subarachnoid hemorrhage using the rat single injection model.

Kv1.5 current State-dependent block of rabbit vascular smooth muscle delayed rectifier and Kv1.5 channels by inhibitors of cytochrome P 450-dependent enzymes. (2001) J. Pharm. Exp. Ther. PDF
    This project examined the direct block of native Kv1.5 in rabbit portal vein (RPV) freshly isolated smooth muscle cells, and Kv1.5 when expressed in isolation in HEK cells. We examined the direct block by various cytochrome P450 inhibitors, demonstrating that well established inhbitors of these enzymes can directly affect potassium channels.
ACh-evoked relaxations of basilar artery

Smooth muscle membrane potential modulates endothelium-dependent relaxation of rat basilar artery via myo-endothelial gap junctions. (2002) J. Physiol. (Lond.) PDF
    We showed for the first time that the effect of 4-AP can be blocked by a gap junction blocker, suggesting a novel mechanism for action of this compound. We suggest that the smooth muscle depolarization induced by block of KdR is transmitted to the endothelium via myoendothelial gap junctions, thus inhibiting eNOS activity and NO production.

Postdoctoral research:
My work is focused on the Cav3.x (T-type) class of calcium channels that are comprised of three distinct subunits: Cav3.1 (G), Cav3.2 (H), and Cav3.3 (I). I am studying the kinetic properties of these subunits when expressed in HEK cells in the context of their function in cerebellar Purkinje and cerebellar deep nuclear neurons.

LPA selectively affects Cav3 calciium channel isoforms The effects of temperature on Cav3.x T-type calcium channels
    In this study we compared the properties of T-type calcium channel isoforms recorded in HEK cells at room temperature vs 37 degrees C to facilitate comparisons to native neuronal currents. The work revealed substantial effects of temperature on the rates of channel activation and inactivation, and in some cases isoform-specific shifts in voltage-dependent properties.
See Iftinca et al. 2006 PDF
LPA selectively affects Cav3 calciium channel isoforms The effects of LPA on Cav3 T-type calcium channels
    Here we show that the endogenous compound lysophosphatidic acid (LPA) activates Rho-associated kinase (ROCK) to differentially regulate Cav3 channel isoforms. LPA decreases Cav3.1 and Cav3.3 current and increases Cav3.2 through a depolarizing shift. These effects were found in expression systems and native retinoblastoma, lateral habenula and DRG neurons.
See Iftinca et al. 2007 PDF
KChiP3 mediated shift in Kv4 inactivation

A Cav3-Kv4 signaling complex regulates A type current and neuronal activity
   A-type potassium channels of the Kv4 family regulate the latency and frequency of spike output in numerous CNS cells. Kv4 channels complex with Potassium Channel Interacting Proteins (KChIPs), a family of calcium sensor proteins that should confer calcium sensitivity. However, neither the physiological source for calcium nor its effects on A-type current were known. Here we show that T-type (Cav3) calcium channels associate with the Kv4 complex to selectively modulate Kv4 inactivation and establish function in a physiological range. See Anderson et al. (2010).

Peer-Reviewed Publications

Uluitu, M, Chris, R. and Iftinca, M. (1999) Influence of acceleration over the hydroelectrolytic homeostasis in audiogenic seizuure-prone rats to normoexcitable rats. Rom. J. Physiology 36 (1-2): 11-27. Pub-Med Link

Iftinca, M., Waldron, G.J., Triggle, C.R. and Cole, W.C. (2001) State-dependent block of rabbit vascular smooth muscle delayed rectifier and Kv 1.5 channels by inhibitors of cytochrome P 450-dependent enzymes. J. Pharmacology Exp. Ther. 298 (2): 718-728. PDF

Allen, T., Iftinca, M., Cole, W.C. and Plane, F. (2002) Smooth muscle membrane potential modulates endothelium-dependent relaxation of rat basilar artery via myo-endothelial gap junctions. J. Physiology (Lond) 545 (Pt 3): 975-986. PDF

Iftinca, M., McKay, B.E., Snutch, T.P., McRory, J.E., Turner, R.W. and Zamponi, G.W. (2006) Temperature dependence of T-type calcium channel gating. Neuroscience 142 (4):1031-1042. PDF

Iftinca, M., Hamid, J., Chen, L., Varela, D., Tadayonnejad, R., Altier, C., Turner, R.W. and Zamponi, G.W. (2007) Regulation of T-type calcium channels by Rho-associated kinase. Nature Neuroscience 10 (7): 854-860. PDF

Kisilevsky, A.E., Mulligan, S.J., Altier, C., Iftinca, M., Varela, D., Tai, C., Chen, L., Hameed, S., Hamid, J., Macvicar, B.A. and Zamponi, G.W. (2008) D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry. Neuron 58(4): 557-70. PDF

Ifinca, M. and Zamponi, G.W. Regulation of neuronal T-type calcium channels. Trends Pharmacol Sci. (2009) 30(1): 32-40.

Anderson, D., Mehaffey, W.H., Iftinca, M., Rehak, R., Engbers, J.D.T., Hameed, S., Zamponi, G.W. and Turner, R.W.  (2010) Regulation of neuronal activity by Cav3-Kv4 channel signaling complexes.  Nature Neuroscience 13: 333-337. Link    Faculty of 1000 citation.

Invited chapters/reviews

Ifinca, M. and Zamponi, G.W. Regulation of neuronal T-type calcium channels. Trends Pharmacol Sci. (2009) 30(1): 32-40.

McKay, B.E., Tadayonnejad, R., Anderson, D., Engbers, J.D.T., Fernandez, F.R.,  Iftinca, M. and Turner, R.W. (2012)  Establishing in vivo like activity in rat cerebellar cells maintained in vitro. In Isolated Central Nervous System Circuits, (Ed K Ballanyi), Neuromethods Series Vol 73 (Ed W Walz). Springer Science+Business Media, LLC, New York, NY, pp 233-262. PDF



Key Abstracts

Waldron GJ, Iftinca M, Clement-Chomienne O, Triggle CR and Cole WC. Direct block of voltage-gated K + current of vascular myocytes by clotrimazole not involving inhibition of cytochrome P 450. Biophys. J . 76: A188, 1999.

Iftinca M, and Cole WC. Cerebral vasospasm after subarachnoid hemorrhage: a wire myograph study.Pharmacologist . 44(2-Suppl. 1): A212, 2002.

Iftinca M, McKay, B.E., McRory, J.E., Turner, R.W. and Zamponi, G.W. Temperature dependence of Cav3 (T-type) calcium channel gating. Biophys. Soc. 2005.

Iftinca, M., Hamid, J., Tadayonnejad, R., Turner, R.W. and Zamponi, G.W. ROCK-mediated inhibition of T-type calcium channels. Biophys Soc. 2007.

Iftinca, M., Anderson, D.M., Rehak, R., Molineux, M.L., Zamponi, G.W. and Turner, R.W. T type calcium channels provide calcium-dependent modulation of A type potassium currents. Can. Assoc. Neurosci. 2008.

Home | Univ. Calgary | Grad Studies | Calgary | Contact Us