Pore-forming a-subunit

BKCa The diversity of BKCa channels can be attributed to the assembly of pore-forming a subunit together with four different auxiliary subunits ((31 -(34). BMS-204352 has been identified as a BKCa channel opener for the treatment of acute ischemic stroke although it has also been shown as an M-channel activator. Therapeutic applications for channel openers include epilepsy, bladder overactivity, asthma, hypertension, and psychosis. Other known BKCa channel openers include NS-8, NS-1619, NS-4, and certain aminoazaindole analogs. 

Molecularly, mammalian voltage-dependent sodium channels are composed of the main pore forming a subunit and smaller auxiliary (3 subunits. The rat brain sodium channel contains the 260-kD a subunit, the 36-kD (31 subunit and the 33-kD (32 subunit. The subunit stoichiometry is a (31 (32 = 1 1 1. 

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... 

As we saw in Chapter 9, sodium channels (Nay channels) consist of a pore-forming a subunit, which is sufficient for functional expression, associated with auxiliary p subunits which modify both the kinebcs and the voltage dependence of channel gabng of the channel. Nine mammalian Nay channel isoforms are known, of which Nayl. 1 and Nayl.3 are predominantly locabsed in neuronal cell bodies and proximal dendrites, where they conbol... 

In 2001, using cryo-electron microscopy and single particle analysis, Sato and colleagues provided the first three-dimensional view of the Nay channel isolated from the eel Electrophorus electricus. The channel was found to have a bell-shaped extracellular surface structure with square-shaped intracellular base and a spherical top (Figure 16.10). In addition to the pore-forming a-subunits, the Nay channels have four additional accessory subunits (Naypi,-Nayp4), each measuring... 

---