(Philadelphia, PA) Using an enzyme found in the venom of the brown recluse spider, researchers at the University of Pennsylvania School of Medicine have discovered a new way to open molecular pores, called ion channels, in the membrane of cells. The research team Zhe Lu, MD, PhD; Yajamana Ramu, PhD; and Yanping Xu, MD, PhD of the Department of Physiology at Penn screened venoms from over 100 poisonous invertebrate species to make this discovery.

The enzyme, sphingomyelinase D (SMase D), splits a lipid called sphingomyelin that surrounds the channel embedded in the cell membrane. As a result, the channel opens to allow the passage of small ions into and out of the cell, thereby generating electrical currents.

The new study, published online earlier this month in the journal Nature, describes how SMase D opens one type of ion channel called a voltage-gated potassium channel (from brain, but experimentally expressed in the membrane of an oocyte, or egg cell) without changing the membrane voltage. The finding introduces a new paradigm for understanding the gating of ion channels and lays the conceptual groundwork for designing new drugs to control ion-channel activity in medical intervention.

Voltage-gated ion channels are embedded in the cell membranes of most types of cells. It has been known for over half a century that the channels open and close in response to changes in electric voltage across the cell membrane, hence their name. In some the cells, (commonly called "excitable"), such as nerve, muscle, heart, and hormone-secreting cells, the channels underlie electrical signaling. They selectively allow the passage of small ions such as sodium, potassium, or calcium into and out of the cell. The precisely controlled passage of ions generates the electrical currents that enable nerve impulse transmission, hormone secretion, and muscle contraction and relaxation. When there are changes to the channel, such as by mutations in a c
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
17-Jul-2006