Potassium channels inward rectifier’ type

Abbreviations 3ARK1, -adrenergic receptor kinase 1 PLC, phospholipase C GIRK, G-protein-activated inwardly rectifying potassium channel Ca(N, P, Q), N-type, P-type, or Q-type calcium channel. 

Potassium ion channels are a veiy diverse family of membrane proteins, with numerous sub-types both in the CNS and peripheral tissues, in particular in the heart. On the basis of the amino acid sequence of the pore-forming a sub-unit, they are classified into two main super-families, the inward rectifier superfamily (which includes receptor-coupled, adenosine 5 -triphosphate (ATP)-sensitive and voltage-dependent channels) and the Sha/cer-related superfamily (which includes Ca2-H-dependent channels). 

The potassium channels present in neuronal membranes could also be affected by phenothiazine derivatives. In the study performed by Ogata et al. [255] it was shown that CPZ (9) interfered with several types of potassium channels present in membranes of neurons of the newborn rat cultured dorsal root ganglia. Reversible reduction of the amplitude was found for transient and delayed rectified K+ currents, while inward rectified K+ current remained unaffected by CPZ (9). The block of delayed rectified K+ current by CPZ (9) was, however, less potent than block of the transient one. The hyper-polarizing shift of the steady-state inactivation curve for transient K+ current indicated that CPZ (9) binds preferably to the channels in the inactivated state. 

D2-like receptors couple mainly to Gi/o proteins, as mentioned above. However, there is no direct evidence to support this coupling for the release-modulating autoreceptors. Moreover, the subsequent intracellular signal transduction has never been studied directly in axon terminals. Mouse AtT-20 pituitary cells, which release acetylcholine and adrenocorticotropic hormone, have been used as a model for axon terminals. When expressed in these cells, D3 receptors mediated inhibition of P/Q-type calcium channels and activation of G protein-coupled inward rectifier potassium channels (Kuzhikandathil et al. 1998 Kuzhikandathil and Oxford 1999). Both would explain the autoreceptor-mediated inhibition of dopamine exocytosis. 

Koyama M, Heerdt PM, Levi R (2003) Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors. Biochem Biophys Res Commun 306 792-6 Koyama S, Brodie MS, Appel SB (2007) Ethanol inhibition of M-current and ethanol-induced direct excitation of ventral tegmental area dopamine neurons. J Neurophysiol 97 1977-85 Kuzhikandathil EV, Yu W, Oxford GS (1998) Human dopamine D3 and D2l receptors couple to inward rectifier potassium channels in mammalian cell lines. Mol Cell Neurosci 12 390 102 Kuzhikandathil EV, Oxford GS (1999) Activation of human D3 dopamine receptor inhibits P/Q-type calcium channels and secretory activity in AtT-20 cells. J Neurosci 19 1698-1707... 

Lovinger DM, Merritt A, Reyes D (1994) Involvement of N- and non-N-type calcium channels in synaptic transmission at corticostriatal synapses. Neurosci 62(1) 31 10 McAllister SD, Griffin G, Satin LS, Abood ME (1999) Cannabinoid receptors can activate and inhibit G protein-coupled inwardly rectifying potassium channels in a xenopus oocyte expression system. J Pharmacol Exp Ther 291(2) 618-26... 

McEachern JC, Shaw CA (1996) An alternative to the LTP orthodoxy a plasticity-pathology continuum model. Brain Res Brain Res Rev 22(1) 51—92 Mackie K, Lai Y, Westenbroek R, Mitchell R (1995) Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. J Neurosci 15(10) 6552—61 Mackie K, Devane WA, Hille B (1993) Anandamide, an endogenous cannabinoid, inhibits calcium currents as a partial agonist in N18 neuroblastoma cells. Mol Pharmacol 44(3) 498-503 Mackie K, Hille B (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci USA 89(9) 3825-9... 

Figure 5.1. Types of potassium channels. Leak channels have four transmembrane helices per subunit, voltage-gated channels (Ky) have 6, and inward-rectifier channels (K. ) have two. The activity of Ky channels is modulated by accessoiy proteins such as KCR-1 and MinK, whereas Kj. channels are controlled by the sulfonylurea receptor. Multiple subtypes exist for all types of channels.

Two types of cannabinoid receptor have so far been identified (reviewed in Howlett et al. 2002). These are CBi, cloned in Tom Bonner s laboratory in the USA in 1990, and CB2, cloned by Sean Munro in the UK in 1993. Both these receptors are coupled through Gi/o proteins, negatively to adenylate cyclase and positively to mitogen-activated protein kinase. CBi receptors are also coupled through Gi/o proteins, positively to A-type and inwardly rectifying potassium channels and negatively to N-type and P/Q-type calcium channels and to D-type potassium channels. In addition, there are reports that CBi and CB2 receptors can enhance intracellular free Ga concentrations (Fan and Yazulla 2003 Rubovitch et al. 2002 Sugiura et al. 1996, 1997, 2000). It is unclear whether this enhancement is Gi/o... 

Guo J, Ikeda SR (2004) Endocannabinoids modulate N-type calcium channels and G-protein-coupled inwardly rectifying potassium channels via CB 1 cannabinoid receptors heterologously expressed in mammalian neurons. Mol Pharmacol 65 665-674... 

Activated CBi receptors can also change fhe function of several types of potassium channels. In oocytes and AtT20 cells artificially expressing the CBi receptor, stimulation of inwardly rectifying potassium channels was repeatedly observed (Henry and Chavkin 1995 Mackie et al. 1995 Garcia et al. 1998 McAllister et al. 1999). Potassium A currents in cultured hippocampal neurons are stimulated by cannabinoids (Deadwyler et al. 1995 Mu et al. 2000). The effects of cannabinoids on potassium M currents in hippocampal brain slices have also been studied M currents were inhibited, which means an enhancement of neuronal excitability (Schweitzer 2000). The potassium K current is inhibited by cannabinoids in cultured hippocampal neurons (Hampson et al. 2000). As in the case of calcium channels, anandamide can elicit a CBi receptor-independent effect on potassium... 

Fast sodium current (/Na) slow calcium current (L-type channels /ca) sodium/calcium exchange current (/Na/Ca) inward potassium rectifier current (/ki) transient currents (7,o) rapid delayed potassium rectifier current (/ks) slow potassium delayed rectifier current (/kt)... 

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