Cellular mechanisms linking electrical and secretory activities of peptide-secretory cells, especially the role of calcium movements in control of secretion.

Recent work used 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.

Recent Publications Seale, A.P., N.H. Richman III, T. Hirano, I.M. Cooke, and E.G. Grau (2003) Cell volume increase and extracellular Ca2+ are needed for hyposmotically induced prolactin release in tilapia. Am. J. Physiol., 284: C1280-C1289.

Seale, A.P., N.H. Richman III, T. Hirano, I.M. Cooke, and E.G. Grau (2003) Evidence that signal transduction for osmoreception is mediated by stretch-activated ion channels in tilapia. Am. J. Physiol., 284: C1290-C1296.

Seale, A.P., I.M. Cooke, T. Hirano, and E.G. Grau (2004) Evidence that IP3 and ryanodine-sensitive intracellular Ca2+ stores are not involved in acute hyposmotically-induced prolactin release in tilapia. Cell. Physiol. Biochem., 14: 155-166.

Selected Earlier Publications 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.

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.

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.

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.

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.

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.

Keller, R., S. Grau, and I.M. Cooke (1995) Quantitation of peptide hormone in single cultured secretory neurons of the crab, Cardisoma carnifex. Cell Tissue Res. 281: 525-532.

Richmond, J.E., E. Sher, and I.M. Cooke (1995) Characterization of the Ca²⁺ current in freshly dissociated crustacean peptidergic neuronal somata. J. Neurophysiol., 73: 2357-2368.

Stuenkel, E., E. Gillary, and I.M. Cooke (1991) Autoradiographic evidence that transport of newly synthesized neuropeptides is directed to release sites in the X-organ - sinus gland of Cardisoma carnifex. Cell Tissue Res. 264:253-262.

Stuenkel, E. L., P. Ruben, I.M. Cooke, and J. Lemos (1990) Sodium-activated channels in peptidergic nerve terminals. Brain Res.,517: 35-43.

Tazaki, K., and I.M. Cooke (1990) Characterization of Ca current underlying burst formation in lobster cardiac ganglion motorneurons. J. Neurophysiol. 63: 370-384.

Cooke, I., R. Graf, S. Grau, B. Haylett, D. Meyers, and P. Ruben (1989) Crustacean peptidergic neurons in culture show immediate outgrowth in simple media. Proc. Nat. Acad. Sci. (U.S.A.) 86:402-406.

Nagano, M., and I.M. Cooke (1987) Comparison of electrical responses of terminals, axons, and somata of a peptidergic neurosecretory system. J. Neurosci. 7:634-648.

Lemos, J. R., J.J. Nordmann, I.M. Cooke, and E. L. Stuenkel (1986) Single channels and ionic currents in peptidergic nerve terminals. Nature 319:410-412.

Cooke, I. M. (1985) Electrophysiological characterization of peptidergic neurosecretory terminals. J. Exp. Biol. 118:1-35.

Theodosis, D. T., P. Legendre, J.-D.Vincent and I.M. Cooke (1983) Immunocytochemically identified vasopressin neurons in culture show slow, calcium-dependent electrical responses. Science 211: 1052-1054.

Invited Reviews

Cooke, I.M. (2002) Physiology of the crustacean cardiac ganglion. K. Wiese (Ed.), The Crustacean Nervous System (Heidelberg, Springer-Verlag), Vol. 2 (in the press).

Cooke, I.M. (2002) Reliable, responsive pacemaking and pattern generation with minimal cell numbers: the crustacean cardiac ganglion. Biol. Bull. 202 (2) (in the press).

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.

Newcomb, R.W., D.K. Hartline, and I.M. Cooke (1988) Changes in information content with physiological history in peptidergic secretory systems. In: D. Ganten and D. Pfaff (Eds.), Current Topics in Neuroendocrinology(Heidelberg, Springer-Verlag), Vol. 9, pp. 151-183.

Stuenkel, E.L., and I.M. Cooke (1988) Electrophysiological characteristics of peptidergic nerve terminals correlated with secretion. In: D. Ganten and D. Pfaff (Eds.), Current Topics in Neuroendocrinology. (Heidelberg, Springer-Verlag), Vol. 9, pp. 123-150.

Cooke, I.M., and R.E. Sullivan (1982) Hormones and neurosecretion. In: H. Atwood and D. Sandeman (Eds.), The Biology of Crustacea. (New York, Academic Press), Vol. 3, Ch. 6, pp. 206-291.

Abstracts on work not published

Xu, S., and I.M. Cooke (2001) Inhibition of crab neuroendocrine calcium current by SNX-482. Soc. Neurosci. Abstr. 27:394.

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.

Richmond, J.E., E. Sher, and I.M. Cooke (1994) Enhancement of calcium currents by a phorbol ester in cultured peptidergic neurons. Soc. Neurosci. Abstr. 20: 902.

Kehoe, J., and I.M. Cooke (1993) Glutamate: possible transmitter role in Aplysia CNS. Soc. Neurosci. Abstr. 19: 922.

Teaching Material

Cooke, I.M., and M. Lipkin, Jr., (1972) Cellular Neurophysiology, A Source Book (N.Y., Holt, Rinehart and Winston), 1039 pp.