Ell action potentials are usually not completely crucial for transmitter secretion. If TRMP5mediated depolarizing present is eliminated by replacing Na with an impermeant cation or by genetic manipulation, receptor cells will still secrete transmitter if they may be depolarized by other means which include elevated K . In addition, if sufficiently depolarized, receptor cells will release transmitter even in the absence of Triadimenol Epigenetic Reader Domain intracellular Ca2 , as shown in the present report and by Romanov et al. (2008). Taste receptor cells secrete transmitter, ATP, by means of gap junction hemichannels, most 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 usually 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 four. Receptor (Type II) cells from TRPM5 knockout mice don’t secrete ATP in response to taste stimulation, but do so when sufficiently depolarized A, simultaneous recordings of Ca2 responses of an isolated receptor cell (Rec, major) isolated from a TRPM5 knockout mouse in addition to a closely apposed ATP PA-Nic Biological Activity biosensor (ATPbio, bottom). The arrows above the traces indicate application of taste mix, KCl or both. Applying taste stimuli evoked a response within the receptor cell but failed to elicit ATP secretion. Having said that, when depolarized with 140 mM KCl, the receptor cell secreted ATP even within the absence of Ca2 mobilization inside the receptor cell. ATP secretion was rescued when taste mix and 50 mM KCl had been coapplied (50 mM KCl alone didn’t trigger ATP secretion, data not shown). B, summary of information from TRPM5 knockout mice. Bars show mean S.E.M. of Ca2 responses in receptor cells (filled bars, best) and concurrent ATP secretion (biosensor cell responses, open bars, bottom). Individual responses had been normalized to the typical in the responses evoked by a manage stimulus of 1 M ATP. N = five experiments, ten 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, makes it possible for ATP secretion through 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 not too long ago reported for caspase1 activation following pannexin 1 activation in main neurons and astrocytes (Silverman et al. 2009). With out voltage clamp measurements, one particular 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.