Conducting sites in excitable membranes

Electrical activity of conducting membranes is produced by transient changes in membrane conductance to Na and K ions. These time- and voltage-dependent conductance changes are controlled by intrinsic proteins that span the membrane and provide a pathway for ion movement. Several lines of evidence indicate that the membrane conducting sites are indeed largely or entirely protein structures. Proteolytic enzymes, when applied on unmyelinated axonal membrane such as the gar olfactory nerve or on eel electroplax, completely destroyed tetrodotoxin (TTX) binding. Treatment of the internal face of the giant axon of the squid with proteases resulted in the loss of the inactivation mechanism of the increased sodium conductance. The binding site of the TTX component in membrane isolated from eel electroplax, estimated by the method of irradiation inactivation, revealed MWs in the range of 230-240 kd. Moreover, this membrane component undergoes a cycle of phosphorylation-dephosphorylation that is affected by electrical activity and various neurotropic compounds and has also been shown to be a protein by the use of proteolytic enzymes. The membrane conducting sites through which ions are flowing are generally called "channels," and the activated "channels" are thought to form "pores" through which ions diffuse according to their electrochemical potential. The channel behaves as though it exists in open or closed permeability or "gating" states. The gating is generally assumed to be solely controlled by the voltage gradient across the membrane. Hence, the denominations of "gating proteins" are often attributed to the specific protein forming the membrane conducting sites. These proteins are intrinsic membrane proteins whose conformational changes, driven by the electric field in the membrane, are responsible for the ion fluxes generating the electrical activity in excitable cells. Electrical excitation of conducting cells involves transient permeability increases to Na+, K+, and Ca+ ions. In some specific cases, Cl-ions may also be involved. These ionic permeabilities are voltage-dependent and can be modified selectively and independently by a variety of compounds, thus leading to the idea that specific entities are spatially separated in the membrane and are acting independently. However, some data of patch-clamp analysis are best interpreted if one assumes that the activation of a specific entity may control the activation of another entity, thereby suggesting a kind of cooperation among some specific ionic sites.(ABSTRACT TRUNCATED AT 400 WORDS)