Research
Interests
Cellular mechanisms linking electrical and secretory activities of
peptide-secretory cells, especially the role of calcium movements
in control of secretion.
Currently, the laboratory is using whole-cell and perforated patch-clamping
techniques together with measurements of cell membrane capacitance,
to characterize the ionic currents, particularly Ca2+, in relation
to exocytotic secretion of prolactin from pituitary cells. The cells
are dissociated from a species of fish having the capability of adapting
to a wide range of salinities, the tilapia Oreochromis mossambicus.
Prolactin functions in adaptation to hypoosmotic conditions and is
released in direct response to reduction of medium osmolality. Further,
in this species, the prolactin-secreting cells are segregated to a
visually distinct lobe of the pituitary, facilitating their isolation.
Imaged microfluorimetry with indicator vital dyes such as fura-2AM
is being used to follow changes of cytoplasmic Ca2+ in these cells
in response to hypoosmotic stimulation.
Earlier work exploited the large neurosecretory terminals of the crab
X-organ - sinus gland to obtain the first intracellular recordings
from secretory terminals; these revealed regenerative Ca2+-mediated
impulses and spike broadening during repetitive activity. Patch-clamping
of the crab secretory neurons in defined primary culture characterized
voltage-gated Ca2+-channels of the somata and the terminals. The technique
of isolating and recording from secretory terminals was later extended
to mammalian neurohypophyseal terminals in other laboratories.
Still earlier work characterized the ionic currents giving rise to
burst-forming potentials in lobster cardiac ganglion motorneurons.
Intrinsic bursting is also a characteristic of many secretory cells.
We found similar currents to those of the cardiac ganglion neurons
responsible for bursting in crab secretory neurons and cultured rat
vasopressin neurons.
[return to top]
Refereed Articles:
Richmond, J.E., A. Codignola, I.M. Cooke, and E. Sher, (1996) Calicum-
and barium-dependent secretion from the rat insulinoma cell line
RINm5F: evidence from capacitance tracking and serotonin release.
Pflügers' Arch., 432: 258-269.
Richmond, J.E., R. Penner, R. Keller, and I.M. Cooke (1996) Characterization
of the Ca2+ current in isolated terminals of crustacean peptidergic
neurons. J. Exp. Biol., 199: 2053-2059.
Meyers, D.E.R. and I.M. Cooke (1997) Comparison of Ca2+ current
of peptidergic neurons developing differing morphology with time
in culture. J. Exp. Biol., 200: 723-733.
Duan, S., and I.M. Cooke (1999) Selective inhibition of transient
K+ current by La3+ in crab peptide-secretory neurons. J. Neurophysiol.,
81: 1848-1855.
Duan, S., and I.M. Cooke (2000) Glutamate and GABA activate different
receptors and Cl- conductances in crab peptide-secretory neurons.
J. Neurophysiol., 83: 31-37.
Perry, A.C.F., T. Wakayama, I.M. Cooke, and R. Yanagimachi (2000)
Mammalian oocyte activation by the synergistic action of discrete
sperm head components: Induction of calcium transients and involvement
of proteolysis. Dev. Biol. 21: 386-393.
Passafaro, M., A. Codignola, M. Rogers, I.M. Cooke, and E. Sher
(2000) Modulation of N-type calcium channels translocation in RINm5F
insulinoma cells. Pharmacological Research, 41: 325-334.
Chung, J.J., L.A. Ratnapala, I.M. Cooke, and A.A. Yanagihara (2001)
Partial purification and characterization of a hemolysin (CAH1)
from Hawaiian box jellyfish (Carybdea alata) venom. Toxicon, 39:
981-990.
[return to top]
Invited Reviews:
Cooke, I.M. (1999) Physiology of mature crustacean neurosecretory
neurons in culture. In: L.W. Haynes (Ed.), The Neuron in Tissue
Culture. (New York, Wiley & Sons), Ch. 18, pp. 261-277.
Cooke, I.M. (2002) Reliable, responsive pacemaking and pattern generation
with minimal cell numbers: the crustacean cardiac ganglion. Biol.
Bull. 202: 108-136.
Cooke, I.M. (2002) Physiology of the crustacean cardiac ganglion.
In: K. Wiese (Ed.), The Crustacean Nervous System (Heidelberg, Springer-Verlag),
Vol. 2 (in the press).
Cooke, I.M. (2002) Physiology of the crustacean cardiac ganglion.
In: K. Wiese (Ed.), Crustacean Experimental Systems in Neurobiology
(Heidelberg, Springer-Verlag), pp. 45-88.
[return to top]
Abstracts:
Duan, S., and I.M. Cooke (1997) La3+ selectively inhibits transient
K+ current (IA) of crab peptide secretory neurons. J. Gen. Physiol.,
110(1): 44a.
Duan, S., and I.M. Cooke (1997) Glutamate and GABA activate different
receptors and Cl- conductances in crab peptide-secretory neurons.
Soc. Neurosci. Abstr. 23(2): 2331.
Rogers, M., J.E. Richmond, P. Sun and I.M. Cooke (1997) GABA receptors
in crab peptidergic secretory neurons and terminals, and their modulation
by Ca2+. Soc. Neurosci. Abstr. 23(1): 375.
Xu, S., and I.M. Cooke (2001) Inhibition of crab neuroendocrine
calcium current by SNX-482. Soc. Neurosci. Abstr. 27:394.
[return to top]
Additional Publications from my laboratory:
Sher, E., A. Codignola, M. Rogers and J. Richmond (1996) Noradrenaline
inhibition of Ca2+ channels and secretion in single patch-clamped
insulinoma cells. FEBS Lett. 385: 176-180.
[return to top]
Research Support at the University of Hawaii (last 5 years)
NIH NS15453-09 to -12, Electrical activity and neurosecretion in
vitro, 7/1/92 - 12/31/98, $365,466 (direct costs).
American Heart Association, Hawaii Chapter, Use-dependent modulation
of Ca2+ channels and secretion in PC12 cells, 7/1/96 - 6/30/98;
$80,000.
The Victoria S. and Bradley L. Geist Foundation, #958935, Mechanism
of action of Hawaiian box jellyfish venom, 1/1/98 - 12/31/98, $36,801.
Queen's Medical Center, #1998-04, Biochemistry and mechanisms of
action of Hawaiian box jellyfish venom, 10/1/98 -12/31/99, $35,000.
Cades Foundation, Grants in support of Research and Training to
the Békésy Laboratory of Neurobiology (Director, P.I.),
annual grants averaging $45,000, since 1997.
[return to top]
|