Profile

Research in the Currie lab is directed toward understanding the function and regulation of voltage-gated calcium channels and calcium-dependent exocytosis, the fundamental cellular mechanism that underlies synaptic transmission and neuroendocrine hormone release. One current focus is the release of catecholamines and other neuroendocrine hormones from adrenal chromaffin cells, central mediators of the sympatho-adrenal stress response (the fight-or-flight response). Chromaffin cells are also a widely used model that enables detailed analyses of stimulus-secretion coupling. G protein coupled receptors (GPCRs) orchestrate precise autocrine / paracrine control of calcium entry and secretion. We are investigating the GPCRs and downstream pathways that are recruited by inflammatory mediators and other paracrine or systemic signals to control transmitter release. In another project (in collaboration with Randy Blakely) we are investigating novel roles for the serotonin transporter (SERT), an important target for antidepressants, in controlling catecholamine secretion. We are also interested in glial regulation of dorsal root ganglion neurons and how this relates to itch / pain signaling (in collaboration with Bruce Carter). We use wild-type and transgenic mice along with a combination of techniques including patch-clamp electrophysiology, carbon fiber amperometry, and fluorescent calcium imaging. Our overall goal is to understand the regulation of calcium channels and transmitter release under physiological conditions, and identify potential therapeutic targets for treatment of nervous and endocrine system disorders in which these finely tuned processes are disrupted.

Publications

Featured publications are shown below:

  1. Sigma-1 receptor ligands inhibit catecholamine secretion from adrenal chromaffin cells due to block of nicotinic acetylcholine receptors. Brindley RL, Bauer MB, Hartley ND, Horning KJ, Currie KPM (2017) J Neurochem
    › Primary publication · 28815595 (PubMed)
  2. Gβγ directly modulates vesicle fusion by competing with synaptotagmin for binding to neuronal SNARE proteins embedded in membranes. Zurawski Z, Page B, Chicka MC, Brindley RL, Wells CA, Preininger AM, Hyde K, Gilbert JA, Cruz-Rodriguez O, Currie KPM, Chapman ER, Alford S, Hamm HE (2017) J Biol Chem
    › Primary publication · 28515322 (PubMed)
  3. Serotonin and Serotonin Transporters in the Adrenal Medulla: A Potential Hub for Modulation of the Sympathetic Stress Response. Brindley RL, Bauer MB, Blakely RD, Currie KP (2017) ACS Chem Neurosci
    › Primary publication · 28406285 (PubMed)
  4. NaV-igating the MAP from PACAP to excitement. Focus on "Activation of MEK/ERK signaling contributes to the PACAP-induced increase in guinea pig cardiac neuron excitability". Currie KP (2016) Am J Physiol Cell Physiol 311(4): C641-C642
    › Primary publication · 27653986 (PubMed) · PMC5129756 (PubMed Central)
  5. An interplay between the serotonin transporter (SERT) and 5-HT receptors controls stimulus-secretion coupling in sympathoadrenal chromaffin cells. Brindley RL, Bauer MB, Blakely RD, Currie KP (2016) Neuropharmacology 110(Pt A): 438-48
    › Primary publication · 27544824 (PubMed) · PMC5028315 (PubMed Central)
  6. "Slow" Voltage-Dependent Inactivation of CaV2.2 Calcium Channels Is Modulated by the PKC Activator Phorbol 12-Myristate 13-Acetate (PMA). Zhu L, McDavid S, Currie KP (2015) PLoS One 10(7): e0134117
    › Primary publication · 26222492 (PubMed) · PMC4519294 (PubMed Central)
  7. Butanol isomers exert distinct effects on voltage-gated calcium channel currents and thus catecholamine secretion in adrenal chromaffin cells. McDavid S, Bauer MB, Brindley RL, Jewell ML, Currie KP (2014) PLoS One 9(10): e109203
    › Primary publication · 25275439 (PubMed) · PMC4183593 (PubMed Central)
  8. A microfluidic platform for chemical stimulation and real time analysis of catecholamine secretion from neuroendocrine cells. Ges IA, Brindley RL, Currie KP, Baudenbacher FJ (2013) Lab Chip 13(23): 4663-73
    › Primary publication · 24126415 (PubMed) · PMC3892771 (PubMed Central)
  9. Regulation of Ca(V)2 calcium channels by G protein coupled receptors. Zamponi GW, Currie KP (2013) Biochim Biophys Acta 1828(7): 1629-43
    › Primary publication · 23063655 (PubMed) · PMC3556207 (PubMed Central)
  10. Gabapentin inhibits catecholamine release from adrenal chromaffin cells. Todd RD, McDavid SM, Brindley RL, Jewell ML, Currie KP (2012) Anesthesiology 116(5): 1013-24
    › Primary publication · 22417967 (PubMed) · PMC3341086 (PubMed Central)
  11. Electrochemical detection of catecholamine release using planar iridium oxide electrodes in nanoliter microfluidic cell culture volumes. Ges IA, Currie KP, Baudenbacher F (2012) Biosens Bioelectron 34(1): 30-6
    › Primary publication · 22398270 (PubMed) · PMC3793634 (PubMed Central)
  12. Regulation of calcium channels and exocytosis in mouse adrenal chromaffin cells by prostaglandin EP3 receptors. Jewell ML, Breyer RM, Currie KP (2011) Mol Pharmacol 79(6): 987-96
    › Primary publication · 21383044 (PubMed) · PMC3102550 (PubMed Central)
  13. G protein modulation of CaV2 voltage-gated calcium channels. Currie KP (2010) Channels (Austin) 4(6): 497-509
    › Primary publication · 21150298 (PubMed) · PMC3052249 (PubMed Central)
  14. Inhibition of Ca2+ channels and adrenal catecholamine release by G protein coupled receptors. Currie KP (2010) Cell Mol Neurobiol 30(8): 1201-8
    › Primary publication · 21061161 (PubMed) · PMC3028936 (PubMed Central)
  15. G protein betagamma subunits modulate the number and nature of exocytotic fusion events in adrenal chromaffin cells independent of calcium entry. Yoon EJ, Hamm HE, Currie KP (2008) J Neurophysiol 100(5): 2929-39
    › Primary publication · 18815342 (PubMed) · PMC2585407 (PubMed Central)
  16. N- and P/Q-type Ca2+ channels in adrenal chromaffin cells. Fox AP, Cahill AL, Currie KP, Grabner C, Harkins AB, Herring B, Hurley JH, Xie Z (2008) Acta Physiol (Oxf) 192(2): 247-61
    › Primary publication · 18021320 (PubMed)
  17. G-proteins modulate cumulative inactivation of N-type (Cav2.2) calcium channels. McDavid S, Currie KP (2006) J Neurosci 26(51): 13373-83
    › Primary publication · 17182788 (PubMed)
  18. Linopirdine modulates calcium signaling and stimulus-secretion coupling in adrenal chromaffin cells by targeting M-type K+ channels and nicotinic acetylcholine receptors. Dzhura EV, He W, Currie KP (2006) J Pharmacol Exp Ther 316(3): 1165-74
    › Primary publication · 16280412 (PubMed)
  19. Etomidate elevates intracellular calcium levels and promotes catecholamine secretion in bovine chromaffin cells. Xie Z, Currie KP, Fox AP (2004) J Physiol 560(Pt 3): 677-90
    › Primary publication · 15331676 (PubMed) · PMC1665276 (PubMed Central)
  20. Role of Cl- co-transporters in the excitation produced by GABAA receptors in juvenile bovine adrenal chromaffin cells. Xie Z, Currie KP, Cahill AL, Fox AP (2003) J Neurophysiol 90(6): 3828-37
    › Primary publication · 12968012 (PubMed)
  21. A 48-hour exposure of pancreatic islets to calpain inhibitors impairs mitochondrial fuel metabolism and the exocytosis of insulin. Zhou YP, Sreenan S, Pan CY, Currie KP, Bindokas VP, Horikawa Y, Lee JP, Ostrega D, Ahmed N, Baldwin AC, Cox NJ, Fox AP, Miller RJ, Bell GI, Polonsky KS (2003) Metabolism 52(5): 528-34
    › Primary publication · 12759879 (PubMed)
  22. Cause for excite-M-ent in adrenal chromaffin cells. Currie KP, Fox AP (2002) J Physiol 540(Pt 3): 729
    › Primary publication · 11986363 (PubMed) · PMC2290266 (PubMed Central)
  23. Differential facilitation of N- and P/Q-type calcium channels during trains of action potential-like waveforms. Currie KP, Fox AP (2002) J Physiol 539(Pt 2): 419-31
    › Primary publication · 11882675 (PubMed) · PMC2290166 (PubMed Central)
  24. Calpains play a role in insulin secretion and action. Sreenan SK, Zhou YP, Otani K, Hansen PA, Currie KP, Pan CY, Lee JP, Ostrega DM, Pugh W, Horikawa Y, Cox NJ, Hanis CL, Burant CF, Fox AP, Bell GI, Polonsky KS (2001) Diabetes 50(9): 2013-20
    › Primary publication · 11522666 (PubMed)
  25. The role of dynamic palmitoylation in Ca2+ channel inactivation. Hurley JH, Cahill AL, Currie KP, Fox AP (2000) Proc Natl Acad Sci U S A 97(16): 9293-8
    › Primary publication · 10900273 (PubMed) · PMC16861 (PubMed Central)
  26. Voltage-dependent, pertussis toxin insensitive inhibition of calcium currents by histamine in bovine adrenal chromaffin cells. Currie KP, Fox AP (2000) J Neurophysiol 83(3): 1435-42
    › Primary publication · 10712470 (PubMed)
  27. Evidence for paracrine signaling between macrophages and bovine adrenal chromaffin cell Ca(2+) channels. Currie KP, Zhou Z, Fox AP (2000) J Neurophysiol 83(1): 280-7
    › Primary publication · 10634871 (PubMed)
  28. Comparison of N- and P/Q-type voltage-gated calcium channel current inhibition. Currie KP, Fox AP (1997) J Neurosci 17(12): 4570-9
    › Primary publication · 9169518 (PubMed)
  29. ATP serves as a negative feedback inhibitor of voltage-gated Ca2+ channel currents in cultured bovine adrenal chromaffin cells. Currie KP, Fox AP (1996) Neuron 16(5): 1027-36
    › Primary publication · 8630241 (PubMed)
  30. Activation of Ca(2+)-dependent Cl- currents in cultured rat sensory neurones by flash photolysis of DM-nitrophen. Currie KP, Wootton JF, Scott RH (1995) J Physiol : 291-307
    › Primary publication · 7714823 (PubMed) · PMC1157729 (PubMed Central)
  31. Aspects of calcium-activated chloride currents: a neuronal perspective. Scott RH, Sutton KG, Griffin A, Stapleton SR, Currie KP (1995) Pharmacol Ther 66(3): 535-65
    › Primary publication · 7494858 (PubMed)
  32. Modulation of neuronal Ca(2+)-dependent currents by neurotransmitters, G-proteins and toxins. Scott RH, Currie KP, Sutton KG, Dolphin AC (1992) Biochem Soc Trans 20(2): 443-9
    › Primary publication · 1383061 (PubMed)
  33. Palmitoyl-DL-carnitine has calcium-dependent effects on cultured neurones from rat dorsal root ganglia. Stapleton SR, Currie KP, Scott RH, Bell BA (1992) Br J Pharmacol 107(4): 1192-7
    › Primary publication · 1334752 (PubMed) · PMC1907908 (PubMed Central)
  34. Calcium-activated currents in cultured neurones from rat dorsal root ganglia. Currie KP, Scott RH (1992) Br J Pharmacol 106(3): 593-602
    › Primary publication · 1324075 (PubMed) · PMC1907550 (PubMed Central)
  35. Activation of Ca(2+)-dependent currents in cultured rat dorsal root ganglion neurones by a sperm factor and cyclic ADP-ribose. Currie KP, Swann K, Galione A, Scott RH (1992) Mol Biol Cell 3(12): 1415-25
    › Primary publication · 1283541 (PubMed) · PMC275709 (PubMed Central)