Ell action potentials usually are not definitely crucial for transmitter secretion. If TRMP5mediated depolarizing current is eliminated by replacing Na with an impermeant cation or by genetic manipulation, receptor cells will still secrete transmitter if they are depolarized by other signifies for instance elevated K . Moreover, if sufficiently depolarized, receptor cells will release transmitter even within the absence of intracellular Ca2 , as shown inside the present report and by Romanov et al. (2008). Taste receptor cells secrete transmitter, ATP, by means of gap junction hemichannels, most likely composed of pannexin 1 (Huang et al. 2007; Romanov et al. 2007; Dando Roper, 2009). Gap junction hemichannels are downstream of TRPM5 and are opened by depolarization and by intracellular Ca2 (Locovei et al. 2006). The Ca2 sensitivity of pannexin 1 hemichannels distinguishes them from connexon gap junction channels. Connexon channels typically are closed by an elevation of intracellular Ca2 (Li et al. 1996). In contrast, pannexin 1 channels are opened by membrane depolarization or by the elevation on the intracellular Ca2 (Bao et al. 2004; Locovei et al. 2006). We conclude that the conjunction of PLC2/IP3 mediated Ca2 release, combined withFigure 4. Receptor (Kind II) cells from TRPM5 knockout mice do not secrete ATP in response to taste stimulation, but do so when sufficiently depolarized A, simultaneous 5 lipoxygenase Inhibitors Reagents recordings of Ca2 responses of an isolated receptor cell (Rec, prime) isolated from a TRPM5 knockout mouse as well as a closely apposed ATP biosensor (ATPbio, bottom). The arrows above the traces indicate application of taste mix, KCl or each. Applying taste stimuli evoked a response within the receptor cell but failed to elicit ATP secretion. On the other hand, when depolarized with 140 mM KCl, the receptor cell secreted ATP even inside the absence of Ca2 mobilization inside the receptor cell. ATP Toloxatone MedChemExpress secretion was rescued when taste mix and 50 mM KCl were coapplied (50 mM KCl alone did not trigger ATP secretion, data not shown). B, summary of information from TRPM5 knockout mice. Bars show imply S.E.M. of Ca2 responses in receptor cells (filled bars, top) and concurrent ATP secretion (biosensor cell responses, open bars, bottom). Individual responses were normalized for the typical on the responses evoked by a handle stimulus of 1 M ATP. N = 5 experiments, 10 cells. P 0.01; P 0.001; Student’s paired t test.2010 The Authors. Journal compilation 2010 The Physiological SocietyCCJ Physiol 588.ATP secretion from taste receptor cellsTRPM5mediated membrane depolarization in receptor cells, allows ATP secretion by means of pannexin 1 hemichannels when taste buds are excited by sweet, bitter and umami taste stimuli. An option explanation for the action of KCl on opening gap junction hemichannels is the fact that K is, itself, acting as a ligand for pannexin 1, independent of its capability to depolarize the cell membrane. This intriguing observation was lately reported for caspase1 activation following pannexin 1 activation in main neurons and astrocytes (Silverman et al. 2009). With out voltage clamp measurements, 1 can not rule out this possibility.
J Physiol 589.21 (2011) pp 5231Muscular effects of orexin A on the mouse duodenum: mechanical and electrophysiological studiesRoberta Squecco, Rachele Garella, Giorgia Luciani, Fabio Francini and Maria Caterina BaccariDipartimento di Scienze Fisiologiche, Universit` di Firenze, Firenze, Italy aThe Journal of PhysiologyNontechnical summary Nervemediated influences o.