Closing of potassium channels

Coupling of the receptors is very similar with all three coupling to Gq and increasing IP3/DAG and in a number of neuronal systems it has been shown that the receptors produce slow depolarising responses via the closing of potassium channels. 

Potassium channels play an important role in the control of insulin secretion in (3-pancreatic cells. In a resting (3-pancreatic cell, the membrane potential is maintained below the threshold for insulin secretion by an efflux of potassium ions through the open potassium channels. As glucose levels rise within the cell, ATP production increases, and the change in the APT/ADP ratio leads to the closing of potassium channels. This causes the calcium channels to open, and entering calcium ions signal insulin secretion. Factors that modulate the (3-pancreatic potassium channels can fine-tune the insulin secretion. 

Synaptic transmission between pairs of neurons in Aplysia (a marine snail) is enhanced by serotonin, a neurotransmitter that is released by adjacent intemeurons. Serotonin binds to a 7TM receptor to trigger an adenylate cyclase cascade. The rise in cAMP level activates PKA, which facilitates the closing of potassium channels by phosphorylating them. Closure of potassium channels increases the excitability of the target cell. 

The mu, delta and kappa opioid receptors are coupled to G° and G proteins and the inhibitory actions of the opioids occur from the closing of calcium channels (in the case of the K receptor) and the opening of potassium channels (for /i, d and ORL-1). These actions result in either reductions in transmitter release or depression of neuronal excitability depending on the pre- or postsynaptic location of the receptors. Excitatory effects can also occur via indirect mechanisms such as disinhibition, which have been reported in the substantia gelatinosa and the hippocampus. Flere, the activation of opioid receptors on GABA neurons results in removal of GABA-mediated inhibition and so leads to facilitation. 

Figure 9.4 Structures of potassium channels in open and closed conformations. The selectivity filter is orange, and the conserved glycine residue is in red. (From Yu et al., 2005. Reproduced with permission of Blackwell Publishing Ltd.)...

Sodium channels spontaneously close and potassium channels begin to open at about this time (see Figure 13.19B). Consequently, potassium ions flow outward, and so the membrane potential returns to a negative value. The resting level of —60 mV is restored in a few milliseconds as the K conductance decreases to the value characteristic of the unstimulated state. Only a very small proportion of the sodium and potassium ions in a nerve cell, of the order of one in a million, flows across the plasma membrane during the action potential. Clearly, the action potential is a very efficient means of signaling over large distances. 

In a nerve cell at rest, the concentration of sodium ions is higher outside the cell than inside. The reverse is true for potassium ions. When a nerve cell is stimulated, sodium channels open and Na ions flood into the cell. A fraction of a second later, the sodium channels close and potassium channels open, allowing K ions to leave the cell. 

Beside arachidonate, a large number of hydrophobic molecules bearing a negatively charged group were found to increase potassium channel activity by contrast, positively charged lipids were found to close the potassium channel. The structures of some lipid molecules shown to activate potassium channels in toad smooth... 

Antidiabetic Drugs other than Insulin. Figure 1 Sulphonylureas stimulate insulin release by pancreatic (3-cells. They bind to the sulphonylurea receptor (SUR-1), which closes Kir6.2 (ATP-sensitive) potassium channels. This promotes depolarisation, voltage-dependent calcium influx, and activation of calcium-sensitive proteins that control exocytotic release of insulin. 

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