周专博士简介

Ionic channels, action potentials and quantal secretion in neuronal cells. Neurotransmitter release is primary triggered by Ca influx during action potentials in neuronal cells. Action potentials are generated and regulated by variety of ion channels on the cell membrane. We are interested in how action potential patterns are regulated by the ion channels, and how secretion is regulated by different encodes of the action potentials. We created a technique for membrane capacitance measurements using reconstituted codes of action potentials as stimulation protocol and we are studying the relation between action potential pattern and cell secretion in chromaffin cells. In dorsal root ganglion (DRG) neurons, we have studied Ca dependence and voltage dependence of exocytosis. We have discovered a Ca independent but voltage dependent secretion (CIVDS) in this sensoring neuron. In superior cervical ganglion (SCG) neurons we are investigating cross talk between nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs). Cell secretion can also be measured by electrochemical micro carbon fiber electrodes (CFE). Combined CFE and patch-clamp recordings allow us to examine the stimulus-secretion-coupling at single synapse/vesicle level in SCG neurons. Other ion channels studied in our lab including Na channel (inactivation), voltage and Ca dependent K channels (specific toxins against BK and SK channels) and HCN pacemaker channels.

Stimulus-secretion-coupling between neurons in the brain slice or living brain. Currently, majority studies on stimulus-secretion-coupling are performed in culture cells. This is because the culture cells offer relative simple techniques to record secretion in single cells. However, interaction between neurons and other cell environment maintain better in brain slice or in vivo. To understand how synaptic transmission and cell secretion occur in brain slice and/or in vivo, we are developing new CFEs and studying neurotransmitter release in slice and in living animals. Our goal is to determining common and different features of the secretion between neurons in culture, in slice or in-vivo. Thus, we are modifying the secretion-recording techniques, which are currently used in culture cells, and applying these techniques to study secretion neurons in brain slices and in living brain.

Calcium homeostasis and secretion in pancreatic islet b-cells. Diabetes is one of the major diseases in China. Abnormal of insulin secretion from -cells is one mechanisms of diabetes. Our goal is to discover physiological and pharmacological mechanisms of ion channels, second messengers, Ca homeostasis and insulin secretion in -cells. We are interested in effects of anesthetics (such as thiopentone) on ion channels, Ca homeostasis and secretion in -cells. We have studied the distinct inactivation of Na channels in -cells. In comparison with chromaffin cells, 85 % of Na channels are inactivated at resting potential in rat -cells. We study -cells by using the techniques adapted from the neuroscience research.

Development of novel microprobes to detect neuropeptides secretion from single cells with high spatial-temporal sensitivity. Neuropeptides are important modulators for fundamental brain functions. Unlike other ligands such as ACh, glutamate etc, there are few neuropeptide-gated ion channels, which can be recorded by patch-clamp. Thus, to detect neuropeptide new probes are needed. Since last 3 years we are working on new types of electrodes, which can sense release of neuropeptides. Our goal is to use the new peptide-electrodes to study how, when and where neuropeptides are released from culture single cells, brain slices and living brains.

Publications

Zhang, C., Xiong, W., Zheng, H., Wang, L., Lu, B., and Zhou, Z. (2004) Calcium- and dynamin-independent endocytosis in dorsal root ganglion neurons. Neuron 42, 225-236

Yu, X., Duan, K., Shang, C., Yu, H., and Zhou, Z. (2004) Calcium Influx through Ih Channels Contributes to Activity-Evoked Neuronal Secretion. Proc. Natl. Acad. Sci. USA, 101: 1051-1056

Duan, K., Yu, X., Zhang C., and Zhou, Z. (2003) Control of Secretion by Temporal Patterns of Action Potentials in Adrenal Chromaffin Cells. J. Neurosci., 23: 11235-11243

Lou, X., Yu, X., Chen, X., He, L., Duan, K., Qu, A., Xu, T., and Zhou, Z. (2003) Na+ channel inactivation: a comparative study between pancreatic islet beta-cells and adrenal chromaffin cells in rat. J. Physiol. (Lond), 548: 191-202

Fan, C., Chen, X., Zhang, C., Wang, L., Duan, K., He, L., Cao, Y., Liu, S., Zhong, M., Ulens, C., Tytgat, J., Chen, J., Chi, C., and Zhou, Z. (2003) A Novel Conotoxin from Conus betulinus, -BtX, unique in Cysteine Pattern and in Function as a specific BK Channel Modulator. J. Biol. Chem., 278: 12624-12633

Ji, Y., Ye, J., Wang, W., He, L., Li, Y., Yan, Y., Li, C., Tan, Z., and Zhou, Z. (2003) Martentoxin, a novel K+-channel-blocking peptide: purification, cDNA and genomic cloning, and electrophysiological and pharmacological characterization. J. Neurochem., 84(2): 325-335.

Bao, L., Jin, S., Zhang, C., Cai, H., Xu, Z., Wang, L., Xiao, H., Ning, F., Zhang, F., Lu, Y., Hokfelt, T., Zhou, Z., and Zhang, X. (2003) Activation of delta-Opioid Receptors on Dorsal Root Ganglion Neurons Induces Receptor Insertion and Neuropeptide Secretion. Neuron, 37: 121-133

Zhang, C. and Zhou, Z. (2002) Ca2+-independent but voltage-dependent secretion in mammalian dorsal root ganglion neurons. Nat. Neurosci., 5(5): 425-430

Song, P., Wang, L., Wang, G., Zhou, Z., and Zhao, Z. (2002) Interleukin-2 regulates calcium current and intracellular calcium via Mu opioid receptors in rat dorsal root ganglion neurons. Neuropharmacology, 43(8):1324-1329

Zhou, Z., and Bers, D. (2002) Time Course of Mitochondrial Antagonists Blockade in Intact Cells. Eur. J. Physiology, 445:132-138