Channel-gating processes

Activation is slower in less depolarized membranes and inactivation drains the open (and resting) state more effectively. In fact, real Na" " channels gate by more complex pathways, including several closed states intermediate between R and O, as well as multiple inactivated states. Inactivation from these intermediate states is probably faster than from / , and the entire activation process, in its fully branched entirety, is rich with kinetic possibilities. However, the effects of toxins may be understood in general by the simpler scheme presented in Figure 2. 

Exactly how this transporter carries noradrenaline across the neuronal membrane is not known but one popular model proposes that it can exist in two interchangeable states. Binding of Na+ and noradrenaline to a domain on its extracellular surface could trigger a conformation change that results in the sequential opening of outer and inner channel gates on the transporter. This process enables the translocation of noradrenaline from the extracellular space towards the neuronal cytosol. 

The mechanisms of the oscillations in biomembranes have been explained based on the gating of membrane protein called an ion channel, and enormous efforts have been made to elucidate the gating process, mainly by reconstitution of channel proteins into bilayer membranes [9-11]. 

The sodium channels consist of a highly processed a subunit (260 kDa) associated with auxiliary p subunits. The pore-forming a subunit is sufficient for functional expression, but the kinetics and voltage dependence of channel gating are modified by the p subunits. The transmembrane organization is shown in Figure 9.5. The a subunit is organized in four... 

Fig. 5. A helical net representation for the inner TM1 helix of Tb MscL illustrating the positions of helix interface residues, pore residues, and gain-of-function mutations. The side chain of Val-21 serves to constrict the channel at the narrowest position. The correspondence between residues at the interface between the inner helices and the gain-of-function mutations is evident (Ou et al., 1998), suggesting this interface is critical for the gating process. Residues 17, 20, 24, and 28 participate in the helix interface with one neighboring TM1 helix, while 18, 22, and 26 participate in the interface with the other neighboring TM1 helix if these residues are found in subunit A, then the former group interacts with subunit E, and the latter with subunit B.

In this chapter we will not address ion conduction proper but we will concentrate on two aspects of ion channels the gating process and the transduction from the initiating stimulus to the operation of the gate. The gating process is the operation of the gate proper while the transducer may be considered the sensor of the stimulus that ultimately opens and closes the channel. Specifically, we will address one type of sensor the membrane potential or voltage sensor. 

Fig. 20. A model of the gating process of alamethicin-like channel formers in a membrane. Explanation in the text...

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