Ion channel modulation and the control of neuronal excitability. We study how the regulation of ion channel function initiates fundamental behaviours. Our focus is a group of neuroendocrine cells that trigger reproduction through a prolonged afterdischarge and release of peptide hormones. Electrophysiology, imaging, and molecular biology are used to examine the role of calcium and non-selective cation channels in controlling excitability and secretion. The work we undertake shows how neuronal and animal behaviour can be altered for extended periods following brief sensory input.
Magoski laboratory - Long-term changes to neuronal excitability and secretion
Many types of neurons display the remarkable property of responding to a transient stimulus with long-term changes to activity, excitability, and/or secretion. This form of plasticity is critical to learning, sensory coding, motor output, and neuroendocrine control.
We use electrophysiology, imaging, and molecular biology to investigate how changes to neuroendocrine cell excitability and peptide release control ovulation in the mollusc, Aplysia californica. This marine snail has been used for almost 50 years to study the cellular and molecular basis of memory, motor pattern generation, defensive reactions, and reproduction, as well as ion channel modulation and function.
Areas of research:
• The control of excitability and secretion by voltage-gated Ca2+ channels and non-selective cation channels.
• Gap junction biophysics and modulation, as well as the role of electrical synapses in shaping neuronal bursting.
Aplysia bag cell neurons:
• In Aplysia (pictured left), the bag cell neurons are found in two clusters in the nervous system and serve as command neurons for egg-laying behaviour.
• These neuroendocrine cells can be examined either in the intact nervous system or, more commonly, as single neurons isolated in primary culture (pictured right).
Bag cell neuron afterdischarge:
• The afterdischarge is a dramatic change in excitability brought about by the concerted action of many ion channels, second messenger systems, and kinases or phosphatases (pictured left as an ensembe extracellular recording from an intact cluster).
• Activity-dependent changes to neuronal excitability can be triggered by both Ca2+ channels and non-selective cation channels (pictured right as a membrane potential recording from a single neuron).
• Of interest is a highly regulated cation channel, permeable to Ca2+, Na+, and K+ ions, that provides excitatory drive for the afterdischarge.
Sturgeon RM, Magoski NS. A closely-associated phospholipase C regulates cation channel function through phosphoinositide hydrolysis. J Neurosci 38:7622-7634. PDF
Beekharry CC, Magoski NS. Protein kinase C enhances electrical synaptic transmission by acting on junctional and postsynaptic Ca2+ currents. J Neurosci 38:2796-2808 (desingated a Featured Article by J Neurosci). PDF
Sturgeon RM, Chauhan AK, Magoski NS. Neuroendocrine control of reproduction in Aplysia by the bag cell neurons. In: Model animals in neuroendocrinology: From worm to mouse to man. Wiley, eds M Ludwig, G Levkowitz, pp 29-58 (peer-reviewed book chapter).
White SH, Sturgeon RM, Gu Y, Nensi A, Magoski NS. Tyrosine phosphorylation determines afterdischarge initiation by regulating an ionotropic cholinergic receptor. Neuroscience 372:273-288. PDF
Magoski NS. Electrical synapses and neuroendocrine cell function. In: Network functions and plasticity: Perspectives from studying neuronal electrical coupling in microcircuits. Elsevier, ed J Jing, pp 137-160 (peer-reviewed book chapter).
Sturgeon RM, Magoski NS. Diacylglycerol-mediated regulation of Aplysia bag cell neuron excitability requires protein kinase C. J Physiol 594:5573-5592. PDF
White SH, Sturgeon RM, Magoski NS. Nicotine inhibits potassium currents in Aplysia bag cell neurons. J Neurophysiol 115:2635-2648. PDF
Groten CJ, Rebane JT, Hodgson HM, Chauhan AK, Blohm G, Magoski NS. Ca2+ removal by the plasma membrane Ca2+-ATPase influences the contribution of mitochondria to activity-dependent Ca2+ dynamics in Aplysia neuroendocrine cells. J Neurophysiol 115:2615-2634. PDF
Beekharry CC, Zhu GZ, Magoski NS. Role for electrical synapses in shaping the output of coupled peptidergic neurons from Lymnaea. Brain Res 1603:8-21. PDF
Groten CJ, Magoski NS. PKC enhances the capacity for secretion by rapidly recruiting covert voltage-gated Ca2+ channels to the membrane. J Neurosci 35:2747-2765. PDF
Dargaei Z, Standage D, Groten CJ, Blohm G, Magoski NS. Ca2+-induced uncoupling of Aplysia bag cell neurons. J Neurophysiol 113:808-821. PDF
Dargaei Z, Phillip L.W. Colmers PLW, Hodgson HM, Magoski NS. Electrical coupling between Aplysia bag cell neurons: characterization and role in synchronous firing. J Neurophysiol 112:2680-2696. PDF
White SH, Carter CJ, Magoski NS. A potentially novel nicotinic receptor in Aplysia neuroendocrine cells. J Neurophysiol 112:446-462. PDF
Akhmedov K, Rizzo V, Kadakkuzha BM, Carter CJ, Magoski NS, Capo TR, and Puthanveettil SV. Decreased response to acetylcholine during aging of Aplysia neuron R15. PLoS ONE 8:e84793 doi:10.1371/journal.pone.0084793. PDF
Hickey CM, Groten CJ, Sham L, Carter CJ, Magoski NS. Voltage-gated Ca2+ influx and mitochondrial Ca2+ initiate secretion from Aplysia neuroendocrine cells. Neuroscience 250:755-772. PDF
Groten CJ, Rebane JT, Blohm G, Magoski NS. Separate Ca2+ sources are buffered by distinct Ca2+ handling systems in Aplysianeuroendocrine cells. J Neurosci 33:6476-6491. PDF
White SH, Magoski NS. Acetylcholine-evoked afterdischarge in Aplysia bag cell neurons. J Neurophysiol 107:2672–2685. PDF
Tam AKH, Gardam KE, Lamb S, Kachoei BA, Magoski NS. Role for protein kinase C in controlling Aplysia bag cell neuron excitability. Neuroscience 179:41-55. PDF
Hickey CM, Geiger KE, Groten CJ, Magoski NS. Mitochondrial Ca2+ activates a cation current in Aplysia bag cell neurons. J Neurophysiol 103:1543-1556. PDF
Tam AKH, Geiger JE, Hung AY, Groten CJ, Magoski NS. Persistent Ca2+ current contributes to a prolonged depolarization in Aplysiabag cell neurons. J Neurophysiol 102:3753-3765. PDF
Geiger JE, Hickey CM, Magoski NS. Ca2+ entry through a non-selective cation channel in Aplysia bag cell neurons. Neuroscience162:1023-1038. PDF
Gardam KE, Magoski NS. Regulation of cation channel voltage- and Ca2+-dependence by multiple modulators. J Neurophysiol102:259-271. PDF
Geiger JE, Magoski NS. Ca2+-induced Ca2+-release in Aplysia bag cell neurons requires interaction between mitochondrial and endoplasmic reticulum stores. J Neurophysiol 100:38-49. PDF
Gardam KE, Geiger JE, Hickey CM, Hung AY, Magoski NS. Flufenamic acid affects multiple currents and causes intracellular Ca2+release in Aplysia bag cell neurons. J Neurophysiol 100:24-37. PDF
Hung AY, Magoski NS. Activity-dependent initiation of a prolonged depolarization in Aplysia bag cell neurons: role for a cation channel. J Neurophysiol 97:2465-2479. PDF
Kachoei BA, Knox RJ, Uthuza D, Levy S, Kaczmarek LK, Magoski NS. A store-operated Ca2+ influx pathway in the bag cell neurons of Aplysia. J Neurophysiol 96:2688-2698. PDF
Lupinsky DA, Magoski NS. Ca2+-dependent regulation of a non-selective cation channel from Aplysia bag cell neurones. J Physiol575:491-506. PDF
Magoski NS, Kaczmarek LK. Association/Dissociation of a channel-kinase complex underlies state-dependent modulation. J Neurosci25:8037-8047 (subsequently featured in a Journal Club: J Neurosci 26:1657-1658). PDF
Zhang Y, Joiner WJ, Bhattacharjee A, Rassendren F, Magoski NS, Kaczmarek LK. The appearance of a PKA-regulated splice isoform of Slo is associated with the maturation of neurons that control reproductive behavior. J Biol Chem 279:52324-52330. PDF
Magoski NS. Regulation of an Aplysia bag cell neuron cation channelby closely associated protein kinase A and a protein phosphatase. J Neurosci 24:6833-6841. PDF
Knox RJ, Magoski NS, Wing D, Barbee SJ, Kaczmarek LK. Activation of a calcium entry pathway by sodium pyrithione in the bag cell neurons of Aplysia. J Neurobiol 60:411-423. PDF
Magoski NS, Kaczmarek LK. Protein kinases and neuronal excitability. In: Encyclopedia of Neuroscience, 3rd edition, CD-ROM Elsevier. G Adelman, BH Smith Eds (peer-reviewed book chapter). PDF
Zhang Y, Magoski NS, Kaczmarek LK. Prolonged activation of Ca2+-activated K+ current contributes to the long-lasting refractory period of Aplysia bag cell neurons. J Neurosci 22:10134-10141. PDF
Magoski NS, Wilson GF, Kaczmarek LK. Protein kinase modulation of a neuronal cation channel requires protein-protein interactions mediated by an Src homology 3 domain. J Neurosci 22:1-9. PDF
Magoski NS, Knox RJ, Kaczmarek LK. Activation of a Ca2+-permeable cation channel produces a prolonged attenuation of intracellular Ca2+ release in Aplysia bag cell neurones. J Physiol 522:271-283. PDF
Magoski NS, Bulloch AGM. Stability and variability of synapses in the adult molluskan CNS. J Neurobiol 42:410-423. PDF
Magoski NS, Bulloch AGM. Dopamine activates two different receptors to produce variability in sign at an identified synapse. J Neurophysiol 81:1330-1340. PDF
Magoski NS, Kaczmarek LK. Direct and indirect regulation of a single ion channel. J Physiol 509:1 (news-and-views).
Magoski NS, Bulloch AGM. Trophic and contact conditions affect synapse formation between identified neurons. J Neurophysiol79:3279-3283.
Wilson GF, Magoski NS, Kaczmarek LK. Modulation of a calcium-sensitive nonspecific cation channel by closely associated protein kinase and phosphatase activities. Proc Natl Acad Sci 95:10938-10943. PDF
Magoski NS, Bulloch AGM. Localization, physiology, and modulation of a molluscan dopaminergic synapse. J Neurobiol 33:247-264. PDF
Nesic O, Magoski NS, McKenny K, Syed NI, Lukowiak K, Bulloch AGM. Glutamate as a putative neurotransmitter in the mollusc, Lymnaea stagnalis. Neuroscience 79:1255-1269. PDF
Magoski NS, Bauce LG, Syed NI, Bulloch AGM. Dopaminergic transmission between identified neurons from the mollusk, Lymnaea stagnalis. J Neurophysiol 74:1287-1300. PDF
Magoski NS, Syed NI, Bulloch AGM. A neuronal network from the mollusc, Lymnaea stagnalis. Brain Res 645:201-213. PDF
Magoski NS, Walz W. The ionic dependence of a P2-purinoceptor mediated depolarization of cultured astrocytes. J Neurosci Res32:530-538.
Magoski NS, Walz W, Juurlink BH. Identification of mouse type-2 astrocytes: demonstration of glutamate and GABA transmitter activated responses. J Neurosci Res 33:91-102.
Walz W, Magoski NS. Short-circuiting effects of K+ currents on electrical responses of type-1-like astrocytes from mouse cerebral cortex. Brain Res 567:120-126. PDF
Potential postdoctoral fellows, graduate students, or undergraduates seeking research opportunities should contact Dr. Magoski directly. The availability of positions depends on the extent to which the laboratory is occupied by more senior students.
Techniques available in the Magoski laboratory
• cell culture (invertebrate neurons, human cell lines)
• molecular biology
• immunocyto and immunohistochemistry
• imaging (intracellular calcium, epifluorescence)
• electrophysiology (single-channel, whole-cell, sharp-electrode, extracellular, capacitance tracking)
Individuals interested should contact Dr. Magoski by email.
Current trainees in my research program (in alphabetical order)
Chauhan, Alamjeet; PhD candidate, Queen’s Experimental Medicine, 8/2015-present.
Gu, Yueling (Angel); MSc candidate Queen’s Neuroscience, 7/2016-present.
MacNeil, Eammon; undergraduate project student, Queen’s Physiology, 7/2018-present.
Wassef, David; MSc candidate, Queen’s Experimental Medicine, 82018-present.
Past trainees in my research program (in alphabetical order)
Aziz, Awsam; undergraduate project student, "Inhibitory effects of dopamine on electrically coupled identified neurons", Queen’s Physiology, 7/2016-6/2017.
Beekharry, Chris; MSc, "PKC activation modulates electrical transmission between Aplysia bag cell neurons", Queen’s Experimental Medicine, 5/2014-12/2016.
Carter, Chris; Postdoctoral Fellow, "Molecular characterization of Aplysia TRP and innexin channels", Queen’s Biomedical and Molecular Sciences, 9/2011-8/2015.
Colmers, Phillip; undergraduate project student, "Electrical coupling in Aplysia bag cell neurons", Queen’s Neuroscience, 7/2010-6/2011.
Dargaei, Zahra; MSc, "Characterization and modulation of electrical coupling between molluscan neuroendocrine cells", Queen’s Physiology, 8/2012-8/2014.
Gardam, Kate; MSc, "Regulation of cation channel voltage- and Ca2+-dependence in Aplysia bag cell neurons", Queen’s Physiology, 5/2006-8/2008.
Geiger, Julia; MSc, "Ca2+ influx and release in Aplysia bag cell neurons", Queen’s Physiology, 8/2005-1/2008.
Groten, Chris; PhD, "The regulation of intracellular Ca2+ and secretion in the bag cell neurons of Aplysia californica", Queen’s Physiology, 5/2009-9/2015.
Hickey, Charlene; MSc, "Ca2+ influx and release controls neuroendocrine cell secretion and excitability", Queen’s Physiology, 6/2007-9/2009.
Hodgson, Heather; technician, Queen’s Biomedical and Molecular Sciences, 10/2011-12/2015.
Hung, Anne; MSc, "Activity-dependent changes in excitability to Aplysia bag cell neurons", Queen’s Neuroscience, 5/2004-9/2006.
Kachoei, Babak; MD work study, "A store-operated Ca2+-influx pathway in Aplysia bag cell neurons", Queen’s Physiology, 5/2003-1/2006.
Lamb, Silas; undergraduate project student, "Protein kinase C translocation influences Aplysia bag cell neuron excitabililty", Queen’s Physiology, 9/2005-4/2006.
Lo, Rebecca; undergraduate project student, "Ca2+ influx and Ca2+ stores feedback regulation of Ca2+ channels", Queen’s Physiology, 9/2011-6/2012.
London, Catherine; technician, Queen’s Biomedical and Molecular Sciences, 11/2015-12/2017.
Lupinsky, Derek; MSc, "Ca2+-dependent regulation of a non-selective cation channel from Aplysia bag cell neurons", Queen’s Physiology, 5/2003-9/2005.
Millete, Jacquline; St. Lawrence College placement student, 1/2004-4/2004.
Nesni, Alysha; undergraduate project student, "Cation channel regulation by tyrosine phosphorylation", Queen’s Physiology, 8/2008-4/2009.
Rebane; Jonathan; undergraduate project student, "Mathematical modelling of intracellular Ca2+ and Ca2+-dependent facilitation of Ca2+ channels in Aplysia bag cell neurons", Queen’s Computing, 5/2012-9/2013 (co-supervised with Dr. G Blohm).
Sham, Lauren; undergraduate project student, "G-proteins influence neuropeptide secretion", Queen’s Physiology, 9/2009-4/2010.
Sloane, Darlene; St. Lawrence College placement student, 1/2006-4/2006.
Smith, Shannon; technician, Queen’s Physiology, 01/6/2002-30/6/2010.
St. Amand, Tim; St. Lawrence College placement student, 1/2007-4/2007.
Sturgeon, Michel; PhD, "Lipid signalling modulates neuroendocrine cell excitability and cation channel function", Queen’s Physiology, 8/2012-9/2018.
Tam, Alan; MD work study, "Role of persisent Ca2+ current in the control of Aplysia bag cell neuron excitability", Queen’s Physiology, 9/2006-6/2009.
White, Sean; PhD, "Cholinergic transmission in molluscan neuroendocrine cells", Queen’s Physiology, 9/2008-8/2013.
Zhu, Tony; undergraduate project student, "Mechanism of rectification at an electrical synapse",Queen’s Physiology, 6/2014-8/2015.
Biomedical & Molecular Sciences Graduate Studies
• field of Experimental Medicine in the Biomedical & Molecular Sciences graduate program.
• graduate coordinator.
Biomedical Sciences 846 - Advanced physiology - Fall, Winter, or Spring/Summer terms (half-class; 3 credits)
• directed studies for graduate students; carried out under the guidance of their graduate supervisor and graduate supervisory committee.
Neurology clinical residence lecture series - Spring term
• a course for Neurology residents to insure post-graduate competency in fundamental neuroscience.
• instructor for action potentials, synaptic transmission, and signalling.
Physiology 215 - Mammalian physiology - Fall term (half-class; 3 credits)
• the function and integration of cells, organs, and body systems.
• instructor for cellular neurophysiology.
Physiology 424 / Biomedical Sciences 824 - Ion channels of excitable membranes - Winter term (half-class; 3 credits)
• the electrophysiology and biophysics of neuronal and cardiac membranes and associated ion channels.
• coordinator and instructor.
Physiology 494 / Biomedical Sciences 894 - Neuroendocrinology - Winter term (half-class; 3 credits)
• selected neuroendocrinology topics, including the control of energy balance, reproduction, and neurosecretory cell excitability and communication.
Physiology or Neuroscience 499 - Undergraduate research project - Fall and Winter terms (two full classes; 12 credits)
• original, wet-lab research in the Magoski laboratory.