Slobodan M. Todorovic
- MD, University of Belgrade School of Medicine
- PhD, University of Illinois
- Residency, Washington University
- Professor, Anesthesiology
- Phone: 924-2283
- Email: email@example.com
Pharmacology and function of T-type (low-voltage-activated, LVA) calcium channels in sensory transmission.
My research interests involve studies of pharmacology and function of voltage-gated calcium channels and particularly T-type (low-voltage-activated, LVA) channels in peripheral and central sensory transmission. Proposed roles for neuronal T-channels include promotion of calcium-dependent burst firing, generation of low-amplitude intrinsic neuronal oscillations, and elevation of calcium entry and boosting of dendritic signals. These channels are taught to contribute to neuronal pacemaker activity, wakefulness, and pain signaling and seizure susceptibility. Despite the fact that these channels were first described in peripheral sensory neurons and the thalamus, their function in sensory processing remains inadequately studied.
My research involves biophysical techniques to measure membrane currents (voltage clamp and current clamp recordings) from acutely dissociated rat sensory neurons and intact brain and spinal cord slices. We have cell lines available that express recombinant ion channel proteins which allow studies of the relationship between structure and function. At the system level, we collaborate with Dr. Jevtovic-Todorovic lab to directly examine the effects of Ca2+ channel modulators on pain sensation following injection into peripheral receptive fields of sensory neurons in intact rats and rats with mechanically (chronic constrictive injury)- or metabolically (diabetic)-induced peripheral neuropathy, as well as knockout mice lacking T-type channels.
Our future studies will investigate how modulation of T-type Ca2+ channels in sensory and CNS neurons affects their function and how different anesthetic, analgesic and anticonvulsant agents selectively target particular classes of voltage-gated Ca2+ channels. In particular, we are interested in testing new selective T-type channel blockers in vitro recordings from DRG and thalamic cells, as well as functional studies of nociception and anesthetic end points in vivo. Our research is funded by NIH research grants from NINDS and NIGMS.
- Orestes P, Bojadzic D, Lee J, Leach E, Salajegheh R, Digruccio M, Nelson M, Todorovic S. Free radical signalling underlies inhibition of CaV3.2 T-type calcium channels by nitrous oxide in the pain pathway. The Journal of physiology. 2010;589 135-48. PMID: 21059758 | PMCID: PMC3039265
- Joksovic P, Weiergräber M, Lee W, Struck H, Schneider T, Todorovic S. Isoflurane-sensitive presynaptic R-type calcium channels contribute to inhibitory synaptic transmission in the rat thalamus. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009;29(5): 1434-45. PMID: 19193890 | PMCID: PMC2659547
- Lee W, Orestes P, Latham J, Naik A, Nelson M, Vitko I, Perez-Reyes E, Jevtovic-Todorovic V, Todorovic S. Molecular mechanisms of lipoic acid modulation of T-type calcium channels in pain pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009;29(30): 9500-9. PMID: 19641113 | PMCID: PMC3073510
- Messinger R, Naik A, Jagodic M, Nelson M, Lee W, Choe W, Orestes P, Latham J, Todorovic S, Jevtovic-Todorovic V. In vivo silencing of the Ca(V)3.2 T-type calcium channels in sensory neurons alleviates hyperalgesia in rats with streptozocin-induced diabetic neuropathy. Pain. 2009;145(1): 184-95. PMID: 19577366 | PMCID: PMC2735619
- Orestes P, Bojadzic D, Chow R, Todorovic S. Mechanisms and functional significance of inhibition of neuronal T-type calcium channels by isoflurane. Molecular pharmacology. 2008;75(3): 542-54. PMID: 19038845 | PMCID: PMC2645928
- Nelson M, Joksovic P, Su P, Kang H, Van Deusen A, Baumgart J, David L, Snutch T, Barrett P, Lee J, Zorumski C, Perez-Reyes E, Todorovic S. Molecular mechanisms of subtype-specific inhibition of neuronal T-type calcium channels by ascorbate. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27(46): 12577-83. PMID: 18003836
- Nelson M, Woo J, Kang H, Vitko I, Barrett P, Perez-Reyes E, Lee J, Shin H, Todorovic S. Reducing agents sensitize C-type nociceptors by relieving high-affinity zinc inhibition of T-type calcium channels. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007;27(31): 8250-60. PMID: 17670971