Disturbances of cochlear blood flow contribute to many clinical hearing conditions. Jiang's laboratory is currently focused on investigation of neurohumoral control mechanisms of inner ear arterioles and the drugs affecting these mechanisms. Using intracellular recording and other techniques on isolated spiral modiolar artery (SMA), we have made a number of novel findings, e.g., 1) SMA cells show unique bi-stable resting potentials (~-40 vs. ~-75 mV), that is mainly due to an all-or-none activation of the inward rectifier potassium channel. Dual cell recording demonstrated that cells with these two RP levels simultaneously exist in the vessel, suggesting a weak gap junction coupling among the muscle and endothelial cells. 2) Stimulation of nervous fibers around the vessel evokes an excitatory junction potential (EJP) in the smooth muscle cells. The EJP is only partially blocked by a- (not b-) receptor antagonists plus a P2X receptor antagonist. Norepinephrine evokes a depolarization in the SMA cells that is also partially resistant to adrenergic-antagonists, suggesting a non-a, non-b adrenergic receptor- mediation of the transmission. 3) Nitric oxide (NO) dilates the SMA and dose-dependently hyperpolarizes both endothelial and muscle cells via activation of ATP- sensitive potassium channels. Further more, the in vitro SMA produces a significant amount of NO that maintains a degree of membrane hyperpolarization and dilation. 4) Endothelium-derived hyperpolarizing factor (EDHF) in the SMA is a complex, involving gap junction coupling and K+-release from the endothelial cells. Ischemia treatment may damage this EDHF mechanism. Future studies will determine the cellular mechanism(s) that causes the bi-stable resting potentials, the action and neurotransmitter role of dopamine, ACh and 5-HT, and the noise-induced pathophysiology in the cochlear artery.

Jiang’s laboratory is also interested in cellular pacemaking mechanism for circadian rhythm in clock neurons of hypothalamic suprachiasmatic nucleus. Developing such a research program is in progress.

	Schematic drawing of the spiral modiolar artery in the cochlea.
	A micrograph of tyrosine hydroxylase (TH) immunohistochemical staining of the SMA in the base turn of the cochlea. Note that TH-positive nerve fibers formed plexus and varicosities around the vessel.

We use acutely isolated spiral modiolar artery (SMA) preparation maintained in a continuously superfused organ bath. Our main techniques are cellular electrophysiological approaches such as intracellular and whole-cell recording methods with current and voltage-clamp analysis. When needed, we also combine intracellular labeling, vaso-diameter tracking and nitric oxide measurement methods. For instance, we may load a cell with fluorescent dye during the electrical recording and then determine the cell type and morphology after the experiment. We use digitized video image and a software to record the micro-vessel diameter and its responses to drugs while an intracellular membrane potential is simultaneously recorded. We also use electrochemical probe to continuously monitor the NO concentration in the organ bath.

Dual cell membrane potential recordings from the SMA. A: Schematic drawing of the experimental settings for B. B depicts the current pulse injection (1 nA, 2 s) to either cell (Electrode 2, E2 for Cell a & E1 for cell b) by balanced bridge mode. The SMA segment was 5 mm long. The current induced a large tonic membrane potential in the injected cells (left, 9.8 mV in cell a; right, 11.6mV in cell b) while produced a small tonic potential in the other cell, revealing a coupling ratio of 14% and 13% in left and right cases, respectively. Note that the traces of cell b, but not of cell a, were low pass (3 kHz) filtered. All traces were an average of 3 sweeps. C: Another pair of cells 0.5 mm apart initially showed a high (cell a) and a low (cell b) RPs and different responses to ACh. After a shift of RP from low to high level (curved arrows) in cell b, both cells showed similar responses to 10 mM K+ and ACh. Key Publications Jiang Z.G., Nuttall A.L., Zhao H., Dai C.F., Guan B.C., Si J.Q., Yang Y.Q., Electrical coupling and release of K+ from endothelial cells co-mediate ACh-induced smooth muscle hyperpolarization in guinea pig inner ear artery. J Physiol (Lond). 564 (2005) 475 - 487. Jiang Z.G., Shi, X.R. Si, J.Q., Zhao H., Nuttall A.L. Basal nitric oxide production contributes to membrane potential and vasotone regulation of guinea pig spiral modiolar artery. Hear Res. 189(2003) 92-100. Si J.Q., Zhao H., Yang Y.Q., Jiang Z.G., Nuttall A.L., Nitric oxide induces hyperpolarization by opening ATP-sensitive K+ channels in guinea pig spiral modiolar artery. Hear Res. 171(2002) 167-176. Jiang Z.-G., Si J.-Q., Lasarev M.R., Nuttall A.L. Two resting potential levels regulated by inward rectifying potassium channels in guinea pig cochlea spiral modiolar artery. J. Physiol (Lond). 537(2001) 829-842. Jiang, Z.G., Qiu, J.H., Ren, T.Y. and Nuttall, A.L. Membrane properties and the excitatory junction potentials in smooth mucle cells of cochlea spiral modiolar artery in guinea pigs. Hearing Res. 138(1999) 171-180. Allen, C.N., Jiang, Z.G., Teshima, K., Darland, T., Ikeda, M., Nelson, C.S., Quigley, D.I., Yoshioka, T., Allen, R.G., Rea, M.A. and Grandy, D.K. Orphanin- FQ/Nociceptin (OFQ/N) modulates the activity of suprachiasmatic nucleus neurons. J. Neuroscience 19(1999) 2152-2160. Jiang, Z.G., Yang, Y.Q., Liou, Z.P. and Allen, C.N. Membrane properties and synaptic inputs of suprachiasmatic nucleus neurons in rat brain slices. J. Physiol.(Lond) 499(1997) 141-159. OHRC Web manager / Electra Allenton / last modified Aug. 3, 2006