Phosphorylation potassium channels

A class of cardiac potassium channels operates in smooth and skeletal muscle, brain, and pancreatic cells. Potassium channels are activated when intracellular ATP levels decrease, and are an important link between the cellular excitability and the metabolic status of the cell. The ratio of ATP/ADP, pH, lactate, and divalent cations determines and modulates the channel activity. The opening of the potassium channels leads to membrane hyperpolarization and a potential decrease as the potassium ions flow out of the cell. Since phosphorylation changes the activity of potassium channels, it modulates cellular excitability. 

The main effect of adrenergic stimulation is to enhance the intracellular adenylyl cyclase activity. This in turn increases cyclic adenosine monophosphate levels. Protein kinase A is activated which modulates, i.e. phosphorylates, calcium and potassium channels. Phosphorylation of the calcium channel increases the inward current leading to early after-depolarization. 

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. 

Regulation of cellular activities by cyclic AMP-dependent protein kinase (PKA) is a critical pathway in neuronal responses via the potassium channel A-current (Childers and Deadwyler 1996). In rat hippocampal cells, PKA phosphorylation of the potassium channel produced a negative shift in the voltage-dependence (Deadwyler et al. 1995). CBi receptor stimulation resulted in a decrease in intracellular cyclic AMP, net dephosphorylation of the channels, activation of the A-type potassium currents, and hyperpolarization of the membrane (Deadwyler et al. 1995 Hampson et al. 1995). The significance of cannabinoid-mediated hyperpolarization of the axon terminals is that it can cause a depression in the response to depolarizing stimuli and failure in neurotransmitter release at the synapse (Childers and Deadwyler 1996). 

In 2003, Offertaler et al. provided further evidence for the endothelial anandamide receptor. Specifically, they reported that a novel cannabidiol analog, 0-1918, opposed the relaxant effects of anandamide and abn-cbd, the in vivo hypotensive effects of abn-cbd, and the phosphorylation of p42/44 MAP kinase induced by abn-cbd in endothelial cells. These actions of 0-1918 were independent of classical cannabinoid and vanilloid receptors, and this led the authors to conclude that 0-1918 was a selective antagonist of the endothelial anandamide receptor. It was suggested that the endothehum-dependent relaxation to abn-cbd and anandamide is G protein coupled to MAP kinase activation and charybdotoxin-sensifive potassium channels but not to nitric oxide. Taken together, the authors proposed that the novel receptor may be coupled to the release of the EDHF. 

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