A. Channels
- Structure and Basic Properties
Channels are multisubunit proteins that span the membrane. They allow passive fluxes of solutes, usually
ions, or water, and in some cases also small solutes such as glycerol and urea [13]. Water channels (aqua-
porins) have been shown to conduct ions in some rare cases, but they are not the subject of this discus-
sion. The tertiary conformation of the main (alpha) subunit of the ion channel creates a hydrophilic pore
across the membrane. A narrow region within the pore forms a “filter” that determines the selectivity of
the channel toward different ions. The selectivity is based on the ion charge and the size, usually of its de-
hydrated form, and its ability to bind (not too tightly) to polar or charged groups in the filter [13,14]. Thus,
there are Kchannels, Ca^2 channels, cation-nonselective channels, anion channels, etc. Gating also con-
trols transport across channels, meaning that various external and internal conditions regulate the confor-
mation of channel proteins, thus affecting the probability that they are in the open state. Some channels
can be gated electrically, by membrane potential [15,16]; other channels chemically, by reversibly bind-
ing specific molecules such as the second messengers, inositol 1,4,5-trisphosphate (IP 3 ) [17]; and yet
other channels mechanically, by membrane stretching [18,19]. Finally, channels differ in their conduc-
tivity. Transport rates through an open channel are relatively high, about 107–108 sec^1 [20], and
100–1000 times higher, per transport unit, than those of carriers [21]. Net fluxes of ions through open
channels can be recorded as electrical current. The “patch-clamp” method permits the recording of such
currents through a single open ion channel or through the sum of the open channels in the membrane of
the whole cell (Figure 1) [22]. The whole-cell current thus depends on the probability of the channels be-
342 JACOBY AND MORANFigure 1 Voltage dependence of Kchannel gating. (A) A linear current-voltage relationship (an I-Vplot)
for a single open ion channel in a plasma membrane patch excised from a protoplast of the mimosa Samanea.
The line represents an “Ohm’s law” for the current through an open ion channel: iK (EMEDM) [22]. The
slope is , the conductance of the single channel. The intersection (marked by an arrow) is EDM, the diffusion
potential of the ions to which the channel is permeable [Eq. 4]. Inset: the excised-patch recording configura-
tion. (B) An I-Vplot for a whole cell (see the recording configuration in the inset). The whole-cell current (IK)
is the sum of the single-channel currents, and the curvature of the I-Vplot represents the increasing number of
channels opening with increased depolarization. (C) An electrical circuit representing the patch-clamp record-
ing configuration. EMis the applied potential difference across the membrane. RMis the resistance (1/conduc-
tance) of the membrane. IKis the current through open Kchannels in the membrane.