Figure 1. Functional and structural properties of voltage-gated sodium and calcium channels. (a) Subunit composition of voltage-gated sodium and calcium channels. (b) Putative organization of the subunit of sodium channels in the membrane. The boxes indicate protein segments that are highly likely to span the membrane. The S4 segment (red) contains a high density of positively charged residues and serves as a voltage sensor. The green loop (P-region) is the major determinant for the ion permeation pathway. The IFM motif (amino acids Ile-Phe-Met) in the cytosolic linker between repeats III and IV is important for the rapid channel inactivation. (c) Voltage-clamp current recordings from mammalian host cells transfected with the µI sodium channel gene from rat skeletal muscle. The current traces are responses to the indicated steps in membrane potential. (d) Peak current versus test voltage from the experiment shown in (c). Note the activation threshold of sodium channels at around –40 mV and the reversal potential for Na⁺ ions close to +50 mV (arrows).

Figure 2. Functional and structural properties of voltage-gated and inward rectifying potassium channels. (a) Subunit composition of voltage-gated (Kv) and inward rectifying (Kir) potassium channels. The channel-forming pores are composed of four subunits (grey). Subunits of Kv channels have a voltage-sensing S4 transmembrane segment that undergoes conformation changes upon changes in the transmembrane electric field inducing closed (left) and open (right) states of the channel pore. Some species of Kv channels associate with cytosolic subunits (left). (b) Putative organization of the subunits of potassium channels in the membrane. Kir channels lack segments S1–S4. (c) Voltage-clamp current recordings from Xenopus laevis oocytes that were injected with mRNA coding for the delayed rectifier channel hKv1.5 (black) and the transient A type potassium channel rKv1.4 (red). (d) The peak currents of the experiments shown in (c) are plotted as a function of test voltage (circles). Also included in this current–voltage plot is a current trace recorded from oocytes expressing the inward rectifier channel mKir2.1 (green). The black and red arrows indicate the activation thresholds for the Kv channels; the green arrow indicates the reversal potential for K channels.

Figure 3. Overview of the gene family of potassium channel-forming protein subunits and related proteins, showing the most important members only (modified after Wei et al., 1996). Based on potassium channels with 2 and 6 transmembrane segments (2TM and 6TM), further channel-forming proteins have presumably evolved by gene duplication and splicing: 2*2TM (TWIK channels), 6+2TM (TOK channels), and 4*6TM (sodium and calcium channels). Several members of the 2TM and 6TM families are indicated. Owing to the rapid progress in the cloning of channel genes, there are many more members expected to be isolated, as indicated by dots.