Inhibition of K 1 channels

In striatal neurons, the effects of D2 receptor activation on K+ channels are more complex. Stimulation of the D2 receptor has been reported to open a K+ channel that displays a 85 pS conductance and a weak inward rectification, and this rectification seems to differ from that found in pituitary cells (Freedman and Weight, 1988 Einhorn et al., 1991 Greif et al., 1995). In contrast, D2 receptor activation was also reported to suppress K+ currents probably through Kir2 channels (Uchimura and North, 1990). However, the activation of K+ channels occurs in a membrane-delimited manner via Gpy mobilization, whereas inhibition of K+ channels could result from the D2 receptor mediated inhibition of adenylyl cyclase and the dephosphorylation of Kir2 subunit at its PKA sensitive site (Nicola et al., 2000). 

A decrease below the threshold Pq, normally close to 50 Torr, in glomus cells of the carotid body or in the neonatal ductus arteriosus results in an inhibition of the tonic K current. Such oxygen-regulated inhibition of K+ channels, which may be mediated by mitochondria-derived hydrogen peroxide (Archer et al., 2004), results in an increase in cellular excitability, increased Ca + influx, and a resultant increase in the level of Ca + in the cytosol (reviewed by Lopez-Barneo et al., 1999). 

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

The ability of morphine to desensitize other neurotransmitter receptors coupled to K+ channels may cause long-term consequences in the activity of neurons. The uncoupling of K+ channel from non-opioid receptors that normally tonically inhibit cell firing could result in an increase in the basal firing of the cells. Changes in the set point of neuronal firing could influence gene expression in the cells and alter the molecular properties of the neurons. 

Inhibition of adenylyl cyclase opening of K+ channels Inhibition of adenylyl cyclase... 

A1 adenosine receptors are inhibitory in the central nervous system. A receptors were originally characterized on the basis of their ability to inhibit adenylyl cyclase in adipose tissue. A number of other G-protein-mediated effectors of A receptors have subsequently been discovered these include activation of K+ channels, extensively characterized in striatal neurons [13], and inhibition of Ca2+ channels, extensively characterized in dorsal root ganglion cells [14]. Activation of A receptors has been shown to produce a species-dependent stimulation or inhibition of the phosphatidylinositol pathway in cerebral cortex. In other tissues, activation of A receptors results in synergistic activation of the phosphatidylinositol pathway in concert with Ca2+-mobilizing hormones or neurotransmitters [15]. The effectors of A adenosine receptors and other purinergic receptor subtypes are summarized in Table 17-2. 

Opioid receptors generally mediate neuronal inhibition. They couple to G or G0> and produce inhibition of Ca2+ channels and opening of K+ channels. They also inhibit adenylyl cyclase. Through this and other downstream signaling pathways, opioid receptors modulate... 

Swartz, K. J., Merritt, A., Bean, B. P., and Lovinger, D. M. (1993) Protein kinase C modulates glutamate receptor inhibition of Ca2+ channels and synaptic transmission. Nature 361,165-168. 

M2 Cardiac M2 Heart, nerves, smooth muscle Seven transmembrane segments, Gj/0 protein-linked Inhibition of cAMP production, activation of K+ channels... 

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