Chapter 10: Distinct Behaviors of Chemical and Voltage Sensitive Gates of Gap Junction Channel

Abstract

Direct cell-to-cell communication is mediated by gap junction channels made of two hemichannels (connexons). Each connexon is composed of six connexins (Cx) radially arranged around the pore. Treatments known to alter cytosolic [Ca 2+ ] i or [H + ] i , and exposure to certain general anesthetics induce channel closure (chemical gating), resulting in cell uncoupling. Gap junction channels are also sensitive to transjunctional voltage (V j ) and transmembrane potential (V m ). Both chemical and voltage gating sensitivities vary among connexins. When V j gradients are applied to poorly coupled cells, the single channel current usually flickers between two or more levels. Over the years, it has been assumed that the channels flicker between a channel open state, γ open , and a closed state. However, recent studies on channel formation in insect and mammalian cells have demonstrated that newly formed channels subjected to V j gradients primarily operate between open and residual conductance states, γ residual , a state in which γ is ∼ 20% of that of the open channel. This suggests that the V j gating mechanism closes the channel only partially. These studies also show that during coupling formation, the first channel opens slowly to γ open , whereas the subsequent transitions between γ open and γ residual are more rapid. A slow kinetics of junctional current (I j ) transitions was also observed during channel gating by V m and lipophilic agents and was believed to reflect the behavior of a second gate, V m -sensitive, distinct from the V j -sensitive gate.