Richard W. Tsien
New York University
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Primary Section: 24, Cellular and Molecular Neuroscience Secondary Section: 23, Physiology and Pharmacology Membership Type:
Member
(elected 1997)
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Research Interests
As a physiologist/neurobiologist, I have long been fascinated by calcium channels. These membrane proteins regulate cellular Ca2+ entry in a voltage-dependent manner and thereby link the realms of electrical signaling and intracellular messengers. A single opening of a Ca2+ channel can allow thousands of calcium ions to enter a cell, thus generating a signal that may control transmitter release, excitability, metabolism, or gene expression. My colleagues and I have been active in discovering and classifying diverse types of Ca2+ channels, including the channels most critical for neurosecretion in the brain. By uncovering N-type Ca2+ channels, we laid the foundation for recent advances in targeting these channels in treatment of certain forms of chronic pain. Our analysis of the biophysical properties of Ca2+ channels led us to propose a mechanism to explain how they manage to be exquisitely selective yet also highly permeant. This mechanism involves high affinity Ca2+ interactions, now worked out at the level of individual amino acid side chains. My colleagues and I have also studied synaptic communication between neurons. Newly developed experimental approaches have allowed us to examine synaptic transmission and plasticity at the level of individual synaptic terminals. We recently found that synaptic activity can cause calmodulin to translocate to the nucleus, thereby activating a transcription factor implicated in long-term memory.
