IK channel

The I channel (K_Ca3.1), which has a conductance of 20–80 pS, is expressed mainly in peripheral tissues such as those of the haematopoietic system, colon, placenta, lung and pancreas. The K_Ca3.1 channel in red blood cells was the first Ca²⁺–sensitive K⁺ channel to be identified and it has been implicated in a wide range of cell functions, including vasodilation of the microvasculature, K⁺ flux across endothelial cells of brain capillaries and the phagocytic activity of neutrophils. K_Ca3.1 is of primary importance in the relationship between K⁺ channels and cell proliferation.

In the latter case, a human hIKCa1 gene encodes the channel found in T cells, which is responsible for the hyperpolarization that is required to keep Ca²⁺ flowing into the cell through the I_CRAC channels.

In comparison with the large-conductance (BK) channels, K_Ca3.1 is much more sensitive to Ca²⁺ and can thus respond to the global level of Ca²⁺. This high affinity for Ca²⁺ depends upon four resident calmodulin molecules tightly bound to the cytoplasmic tails of the four pore-forming α-subunits. Before the channel can open, Ca²⁺ must bind to each of the calmodulins to induce the co-operative conformational change that opens the gate, which explains why this process has a Hill coefficient of 4. This Ca²⁺–induced gating process resembles that which has been described for the small-conductance (SK) channels. The fact that calmodulin is prebound to its effector enables the channels to respond to Ca²⁺ very quickly.

The PtdIns3P signaling cassette may play a role in regulating the activity of K_Ca3.1. If this signaling lipid is hydrolysed by MTMR6, which is one of the myotubularins, there is a decrease in the activity of the Ca²⁺–activated channel.

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