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 channel
gene, disease can result. For example,
mutations in some channel genes cause
cardiac arrhythmias, including a form of
the lethal long QT syndrome.
Voltage-gated ion channels are also
present in the so-called non-excitable
cells (such as immune, blood, and bone
cells) whose membrane voltage stays
largely constant, as opposed to the
excitable cells whose membrane voltage
constantly varies in a precisely
controlled manner. How the activity of
channels in non-excitable cells is
regulated has been a long-standing
biological mystery. This new finding that
SMase D can open ion channels without
changing membrane voltage provides a clue
to the mystery.
This work was supported by a research
grant from the National Institutes of
Health.
Source: University of Pennsylvania School of Medicine
Published on 25th
JULY 2006
