Miduturu Srinivas, PhD

Miduturu Srinivas, PhD
SUNY College of Optometry
33 West 42nd Street
New York, NY 10036

Research in our laboratory is focused on biophysical and physiological studies of gap junctions, which are intercellular channels that facilitate communication between adjacent cells by allowing the passage of ions, second messengers and important metabolites. We study the function of gap junctions in the crystalline lens. Major studies pertaining to lens physiology are directed at resolving: 1) the role of gap junctions in the establishment of a reducing environment in the lens nucleus by providing a pathway for transport of molecules such as anti-oxidants and associated co-factors, 2) whether alteration in conductance and permeability properties of these channels leads to cataract formation that occur due to age or due to mutations in genes encoding connexins, the proteins that form gap junction channels and 3) the structural determinants that underlie permeation and gating of lens gap junctions. We also have a long-standing interest in the identification of modulators of connexin channels. Current studies are aimed at developing faster screening strategies to identify novel inhibitors and channel openers. The feasibility of newer agents to potentially reverse the changes in connexin channel function and the pathological changes observed in cataractogenesis is also a current avenue of research. Our studies utilize a variety of techniques including patch clamp recording of single channels and whole cell currents from transfected cells and from primary cells obtained from genetically-engineered mice with altered levels of connexin expression, microinjection of probes into lens fibers, generation and characterization of cell-specific connexin knockouts, and standard methods such as RT-PCR, immunostaining and Western blot analyses.

Pharmacy, Birla Institute of Technology and Science, BA, 1991
University of Florida, PhD Pharmacology, 1992-1997

  • 1991 Research Assistant, Department of Pharmacology, Central Drug Research Institute, Lucknow, India
  • 1992-1997 Graduate Assistant, Department of Pharmacology, University of Florida, Gainesville, FL
  • 1997-2001 Research Associate, Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY
  • 2001-2004 Instructor Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY
  • 2004 Assistant Professor, Department of Biological Sciences, SUNY College of Optometry, New York, NY
  • 1999 Grass Fellow, Marine Biology Laboratory, Woods Hole, MA
  • 2000 K. Hartline/S.W. Kuffler/F.R. Lillie Fellow, Marine Biology Laboratory, Woods Hole, MA

Belardinelli, L., Shryock, J.C., Song, Y., Wang, D., and Srinivas, M.: Ionic basis for the electrophyisological actions of adenosine in cardiomyocytes. FASEB J. 9:359-365, 1995.
Srinivas, M., Shryock, J.C., Scammells, J.C., Ruble, J., Baker, S.P., Belardinelli, L.: A novel irreversible antagonist of the A1-adenosine receptor. Mol. Pharmacol. 50:196-205, 1996.
Song, Y., Srinivas, M., Belardinelli, L.: Nonspecific inhibition of adenosine-activated K current by glybenclamide in guinea pig atrial myocytes. Am. J. Physiol. 271:H2430-H2437, 1996.
Srinivas, M., Shryock, J.C., Baker, S.P., Dennis, D.M., Belardinelli, L.: Differential A1-adenosine receptor reserve for two actions of adenosine in the guinea pig atria. Mol. Pharmacol. 52:683-691, 1997.
Srinivas, M, Rozental R., Kojima T., Dermeitzel R., Mehler M., Condorelli D. F., Kessler J. A., Spray D.C. Functional properties of channels formed by the neuronal gap junction protein connexin36. J Neurosci.19 (22):9848-55, 1999.
Srinivas, M., Costa M., Fort A., Fishman G.I., Spray D.C: Voltage dependence of macroscopic and unitary currents of gap junction channels formed by mouse connexin50 expressed in rat neuroblastoma cells. J Physiol (Lond).517 ( Pt 3):673-89, 1999.
Spray, D.C., Suadicani, S.O., Vink, M.J. and Srinivas, M. (2000) Gap junction channels and healing over of injury. In: Heart Physiology and Pathophysiology. N. Sperelakis, Y Kurachi, et al., eds., Academic Press, N.Y, pp. 149-174.
Rozental, R., Srinivas, M., Gokhan, S., Urban, M., Dermietzel, R., Kessler, J.A., Spray, D.C. and Mehler, M.F. (2000) Temporal expression of neuronal connexins during hippocampal ontogeny. Brain Res. Rev 32:57-71.
Hopperstad, M.G., Srinivas, M., and Spray, D.C. (2000) Properties of gap junction channels formed by Cx46/Cx50 gap junction channels. Biophys J. 79(4):1954-66.
Dermietzel R, Kremer M, Paputsoglu G, Stang A, Skerrett IM, Gomes D, Srinivas M, Janssen-Bienhold U, Weiler R, Nicholson BJ, Bruzzone R, Spray DC (2000). Molecular and functional diversity of neural connexins in the retina. J Neurosci. 20(22):8331-43.
Rozental, R., Srinivas, M., and Spray, D.C. (2001).How to close a gap junction channel: Efficacies and potencies of uncoupling agents. Methods Mol Biol.154: 447-76.
Srinivas, M., Hopperstad M.G., Spray DC (2001). Quinine blocks specific gap junction channel subtypes. Proc Natl Acad Sci. 98(19):10942-47.
De Pina-Benabou, M.H., Srinivas, M., Spray, D.C., and Scemes, E. (2001) CaM kinase pathway mediates the K+induced increase in gap junctional communication between mouse spinal cord astrocytes. J. Neurosci. Sept 1; 21(17):6635-43.
Spray, D.C., Suadicani, S.O., Srinivas, M., and Fishman, G.I.. (2002). Gap junctions in the cardiovascular system. In E.Page, H.A. Fozzard and R.J. Solaro (Eds.) Handbook of Physiology, Section 2: The Cardiovascular System, Vol I: The Heart, Oxford University Press Chapter 4, pp169-212.
Kojima, T., Srinivas, M., Fort, A., Urban, M., Lee, G-H., Sawada, N., and Spray, D.C. (2001) Growth-suppressive function of human connexin32 in a conditional immortalized mouse hepatocyte cell line. In Vitro Cell. Dev. Biol. 37:589-598.
Zoidl, G. Meier, C., Petrasch-Parwez, E., Zoidl, C., Habbes, H.-W., Kremer, M., Srinivas, M., Spray, D.C., and Dermietzel, R. (2002) Evidence for a role of the N-terminal domain of the neuronal connexin36 (Cx36) in subcellular localization. J Neurosci Research, 69 (4); 448-465.
White T. W., Srinivas M., Ripps H., Trovato-Salinaro A., Condorelli D. F., Bruzzone R. (2002) Virtual cloning, functional expression, and gating analysis of human connexin31.9. Am J Physiol Cell Physiol. 283(3):C960-70.
Spray, D.C., Rozental, R., Srinivas, M. (2002) Prospects for rational development of pharmacological gap junction channel blockers. Current Drug Targets 3(6):455-64.
Srinivas M., and Spray D.C. (2003). Closure of gap junction channels by arylaminobenzoates. Mol Pharmacol 63(6):1389-97.
Zoidl G, Bruzzone R, Weickert S, Kremer M, Zoidl C, Mitropoulou G, Srinivas M, Spray DC, Dermietzel R. (2004). Molecular cloning and functional expression of zfCx52.6: a novel connexin with hemichannel-forming properties expressed in horizontal cells of the zebrafish retina. J Biol Chem. 279(4):2913-21.
Srinivas M, Duffy HS, Delmar M, Spray DC. (2004) Pharmacological approaches to block gap junctions. In Cardiac Electrophysiology; From Bench to Bedside (Eds Zipes and Jalife).
Cruikshank S, Hopperstad M, Younger M, Connors B, Spray DC , Srinivas M (2004). Potent block of Cx36 and Cx50 gap junction Channels by mefloquine. Proc Natl Acad Sci U S A. 101(33):12364-9.
Srinivas M, Kronengold J, Bukauskas FF, Bargiello TA, Verselis VK. (2005) Correlative Studies of Gating in Cx46 and Cx50 Hemichannels and Gap Junction Channels. Biophys J. 88(3):1725-39
Nicchia GP, Srinivas M, Li W, Brosnan CF, Frigeri A, Spray DC. (2005) New possible roles for aquaporin-4 in astrocytes: cell cytoskeleton and functional relationship with connexin43. FASEB J. 19(12):1674-6.
Srinivas M, Calderon DP, Kronengold J, Verselis VK. (2006) Regulation of connexin hemichannels by monovalent cations. J Gen Physiol 127(1):67-75.
DeRosa AM, Mui R, Srinivas M, White TW (2006). Functional characterization of a naturally occurring Cx50 truncation. Invest Ophthalmol Vis Sci. 47(10):4474-81.
Bai D, Del Corsso C, Srinivas M, Spray DC (2006). Block of specific gap junction channel subtypes by 2-aminoethoxydiphenyl borate (2-APB). J Pharmacol Exp Ther. 319(3):1452-8
Martinez-Wittinghan FJ, Srinivas M, Sellitto C, White TW, Mathias RT. (2006) Mefloquine effects on the lens suggest cooperative gating of gap junction channels. J Membr Biol. 211(3):163-71.

2002-2005:
Block of Lens and Neuronal Gap Junctions by Quinine, National Eye Institute, National Institutes of Health
RO1 (EY13869) (Miduturu Srinivas, P.I)
The goal of this project is to determine and characterize the block of gap junction channels by quinine and its derivatives.
Role: P.I.

2005-2009:
Block of Lens and Neuronal Gap Junctions by Quinine, National Eye Institute, National Institutes of Health
RO1 (EY13869) (Miduturu Srinivas, P.I)
The goal of this project is to use mefloquine to study the function of Cx50 in the lens.
Role: P.I.