**2. Proteins that form large channels in mammal cells**

These large channels are distinguished by their proteins which can be classified in accordance with their function, mechanism for membrane penetration, the size of their pores, its pore-forming subunits, and type of pore-forming proteins within the membrane plane (α- or β). By comparing the protein configuration in the plasma membrane it is possible to actually evolutionarily delineate the pore-forming protein of distinct organisms.

Proteins that form large conductance channels in the plasma membrane have been described in virus (Madan et al, 2007), bacteria (Huffman et al, 2004), fungi (Ojcius, D. M. & Young, J. D., 1991) and plantae (Klüsener & Weiler, 1999). Mostly due to these proteins being functionally linked to the mechanism of defense (plantae) or the invasion of the hosts (virus, bacteria, etc). These proteins are often secreted into the extracellular environment as monomers which then oligomerize and form the channel in the host membrane.

In humans and other mammals the secreted proteins, there have been found the antimicrobial peptide families of defensins (Kagan et al 1990) and cathelicidins (Scocchi et al, 1999; Skerlavaj et al, 2001). Other peptides, such as dermicidin (Boman et al 1993; Christensen et al, 1988) and anionic peptides (Brogden et al, 1996,1997,2003) are also found in tissue-specific areas. In the immune system, these pores cause physical damage to invading pathogens. In general, pore-forming proteins are monomeric molecules that interact with each other while they are inserted into membranes, where they continue to polymerize further to form large transmembrane pores, leading to a process of antimicrobial activity and cytotoxicity.

Generally, in vertebrates, more specifically in mammals, these pores are integral membrane proteins that are capable of opening under physiological or pathological condition. They can be found in several parts of the organism and may be associated with organism defense (release of pro-inflammatory agents, destruction of pathogens, cell death) or not (release of neurotransmissor, proliferation etc).

The main large conductance ion channels which are found in mammals, are the connexin hemichannels (Cx43, Cx32 and other), pannexins (pannexin-1), maxi anion channel, voltagedependent anionic channel (VDAC), maxi-K channel, maitotoxin pore, transient receptor potential vanilloid type-1 (TRPV1), transient receptor potential ankhirin type-1 (TRPA1) and ATP-activated P2X pores (P2X2, P2X4 and P2X7 receptors). All of these permit the passage of mono and divalent ions and the flow of molecules of up to 1000 Da. The majority of these large conductance ion channels are preferentially permeable to cations, while VDAC and maxi anion are permeable to anions. In addition, they are all permeable to the anionic ATP4 molecule (Nagasawa et al, 2009; Pellegatti et al, 2005; Yip et al, 2009) and glutamate (Léon et al, 2008).
