TRPC4 currents have properties similar to the pacemaker current in interstitial cells of Cajal

2002 ◽  
Vol 283 (6) ◽  
pp. C1637-C1645 ◽  
Author(s):  
Rebecca L. Walker ◽  
Sang Don Koh ◽  
Gerard P. Sergeant ◽  
Kenton M. Sanders ◽  
Burton Horowitz
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Single Channel ◽  
Interstitial Cells ◽  
Cation Channels ◽  
Pacemaker Current ◽  
Whole Cell ◽  
Cation Current ◽  
Nonselective Cation Channels ◽  
Nonselective Cation Current ◽  
Cells Of Cajal

Interstitial cells of Cajal (ICC) are the pacemaker cells responsible for the generation and propagation of electrical slow waves in phasic muscles of the gastrointestinal (GI) tract. The pacemaker current that initiates each slow wave derives from a calcium-inhibited, voltage-independent, nonselective cation channel. This channel in ICC displays properties similar to that reported for the transient receptor potential (TRP) family of nonselective cation channels, particularly those seen for TRPC3 and TRPC4. We have identified transcripts for TRPC4 in individually isolated ICC and have cloned the two alternatively spliced forms of TRPC4, TRPC4α and TRPC4β, from GI muscles. TRPC4β is missing an 84-amino acid segment from the carboxy terminus. Expression of either form using the whole cell patch-clamp technique led to calcium-inhibited, nonselective cation channels as determined by N-methyl-d-glucamine replacement experiments and BAPTA dialysis. Expression of TRPC4β channels recorded at the whole cell level had characteristics similar to the nonselective cation current in ICC. The single-channel conductance of TRPC4β was determined to be 17.5 pS. Application of calmidazolium to cells expressing TRPC4β led to a significant increase in the inward current of these cells at both the whole cell and single-channel level, and currents were sensitive to block by 10 μM lanthanum, niflumic acid, and DIDS. Comparison of the properties reported for the nonselective cation current in ICC and those identified here for TRPC4β led us to conclude that a TRPC4-like current encodes the plasmalemmal pacemaker current in murine small intestine.

scholarly journals Caffeine inhibits nonselective cationic currents in interstitial cells of Cajal from the murine jejunum

2009 ◽  
Vol 297 (4) ◽  
pp. C971-C978 ◽  
Author(s):  
Nan Ge Jin ◽  
Sang Don Koh ◽  
Kenton M. Sanders
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Equilibrium Potential ◽  
Cation Channels ◽  
Pacemaker Activity ◽  
Dependent Manner ◽  
Current Clamp ◽  
Concentration Dependent Manner ◽  
Nonselective Cation Channels ◽  
Cells Of Cajal

Interstitial cells of Cajal (ICC) discharge unitary potentials in gastrointestinal muscles that constitute the basis for pacemaker activity. Caffeine has been used to block unitary potentials, but the ionic conductance responsible for unitary potentials is controversial. We investigated currents in cultured ICC from murine jejunum that may underlie unitary potentials and studied the effects of caffeine. Networks of ICC generated slow wave events under current clamp, and these events were blocked by caffeine in a concentration-dependent manner. Single ICC generated spontaneous transient inward currents (STICs) under voltage clamp at −60 mV and noisy voltage fluctuations in current clamp. STICs were unaffected when the equilibrium potential for Cl− ( ECl) was set to −60 mV (excluding Cl− currents) and reversed at 0 mV, demonstrating that a nonselective cationic conductance, and not a Cl− conductance, is responsible for STICs in ICC. Caffeine inhibited STICs in a concentration-dependent manner. Reduced intracellular Ca2+ and calmidazolium (CMZ; 1 μM) activated persistent inward, nonselective cation currents in ICC. Currents activated by CMZ and by dialysis of cells with 10 mM BAPTA were also inhibited by caffeine. Excised inside-out patches contained channels that exhibited spontaneous openings, and resulting currents reversed at 0 mV. Channel openings were increased by reducing Ca2+ concentration from 10−6 M to 10−8 M. CMZ (1 μM) also increased openings of nonselective cation channels. Spontaneous currents and channels activated by CMZ were inhibited by caffeine (5 mM). The findings demonstrate that the Ca2+-inhibited nonselective cation channels that generate STICs in ICC are blocked directly by caffeine. STICs are responsible for unitary potentials in intact muscles, and the block of these events by caffeine is consistent with the idea that a nonselective cation conductance underlies unitary potentials in ICC.

Interstitial cells of Cajal generate a rhythmic pacemaker current

1998 ◽  
Vol 4 (7) ◽  
pp. 848-851 ◽  
Author(s):  
Lars Thomson ◽  
Tim L. Robinson ◽  
Jonathan C.F. Lee ◽  
Laura A. Farraway ◽  
Martin J.G. Hughes ◽  
...  
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Current ◽  
Cells Of Cajal

Cyclic nucleotide-gated cation channels mediate sodium absorption by IMCD (mIMCD-K2) cells

1997 ◽  
Vol 272 (3) ◽  
pp. C901-C910 ◽  
Author(s):  
D. H. Vandorpe ◽  
F. Ciampolillo ◽  
R. B. Green ◽  
B. A. Stanton
Keyword(s):  
Patch Clamp ◽  
Single Channel ◽  
Collecting Duct ◽  
Single Cells ◽  
Cation Channels ◽  
Sodium Absorption ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Nonselective Cation Channels ◽  
Na Currents

The inner medullary collecting duct cell line, mIMCD-K2, absorbs Na+ by an amiloride-sensitive, electrogenic mechanism. The goal of the present study was to characterize the amiloride-sensitive, Na+ -conducting channels responsible for electrogenic Na+ absorption. To this end, we measured Na+ currents in single cells with the patch-clamp technique and Na+ currents across monolayers mounted in Ussing-type chambers. In whole cell patch-clamp experiments, amiloride-sensitive, inward Na+ currents were mediated by nonselective cation channels. In single-channel patch-clamp experiments, amiloride- and guanosine 3',5'-cyclic monophosphate (cGMP)-sensitive, 20-pS nonselective cation channels (i.e., CNG channels) were identified in the apical membrane. CNG channels were inhibited by amiloride, diltiazem, ethylisopropylamiloride (EIPA), and 8-bromo-cGMP and were permeable to Ca2+ and Mg2+. Epithelial Na+ channels were never observed in whole cell or single-channel recordings. Na+ absorption across confluent monolayers was inhibited with a rank order potency of benzamil > amiloride > phenamil >> EIPA > diltiazem. Our data are most consistent with the view that CNG channels mediate electrogenic Na+ absorption across mIMCD-K2 cells.

Phosphorylation-dependent regulation of nonselective cation channels in guinea pig chromaffin cells

1993 ◽  
Vol 265 (2) ◽  
pp. C343-C348 ◽  
Author(s):  
M. Inoue ◽  
I. Imanaga
Keyword(s):  
Guinea Pig ◽  
Chromaffin Cells ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Cation Channels ◽  
Dependent Manner ◽  
Cation Current ◽  
Nonselective Cation Channels ◽  
Nonselective Cation Current ◽  
External Signals

In guinea pig chromaffin cells, acetylcholine induces a nonselective cation current by activating a muscarinic receptor, probably m4. We investigated activation and deactivation processes of this current. The calmodulin antagonists trifluoperazine and calmidazolium reversibly suppressed the muscarinic activation of the nonselective cation current in a dose-dependent manner; the former was about six times less potent than the latter. H-7, a kinase inhibitor, also reversibly inhibited the muscarinic current with a concentration eliciting 50% of maximal inhibition of 277 microM. Internal application of vanadate, a nonspecific phosphatase inhibitor, enhanced the muscarinic current and markedly slowed the time course of its deactivation, but the phosphatase 1 and 2A inhibitors okadaic acid and calyculin A had no effects. Lowering Mg2+ concentration in the patch solution mimicked the effects of vanadate on the muscarinic current. Internal dialysis with vanadate or low-Mg2+ solution gradually led to development of an inward current, and the related voltage dependence was similar to that seen with the muscarinic cation current. These results suggest that kinase and Mg(2+)-dependent phosphatase are responsible for activation and deactivation of nonselective cation channels. The channels seem to be under the influence of both enzymes, even in the absence of external signals.

Sodium current in human small intestinal interstitial cells of cajal

2001 ◽  
Vol 120 (5) ◽  
pp. A201-A201 ◽  
Author(s):  
P STREGE ◽  
A RICH ◽  
Y OU ◽  
S GIBBONS ◽  
M SARR ◽  
...  
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Sodium Current ◽  
Interstitial Cells ◽  
Small Intestinal ◽  
Cells Of Cajal

Effects of Morphine on Interstitial Cells of Cajal in Rabbit Colon and Small Intestinal Transit: An Experimental Study

2020 ◽  
Vol 20 (3) ◽  
pp. 240-246
Author(s):  
Heng Yang ◽  
Xiao-Ju Jin ◽  
Hong Luo ◽  
Yuan-Hai Li
Keyword(s):  
Protein Expression ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Saline Control ◽  
Morphine Group ◽  
Small Intestinal Transit ◽  
Medium Concentration ◽  
Epidural Puncture ◽  
Mrna And Protein Expression ◽  
Cells Of Cajal

Objective: This study aims to investigate the effect of morphine with naloxone on intestinal peristalsis and the number of interstitial cells of Cajal (ICC) in colon tissues of rabbits. Methods: Thirty rabbits were randomly divided into five groups (n=6, each group): saline control group (NS group), low concentration of morphine group (L group), medium concentration of morphine group (M group), high concentration of morphine group (H group), medium concentration of morphine and naloxone mixed with antagonist group (NM group). Rabbits in these five groups were administered with an epidural puncture tube and dorsal epidural analgesia pump, and were continuously infused for seven days. Fecal characteristics were observed, and the ink propulsion rate was calculated. The expression level of ICC C-kit protein in colon tissues was tested by western blot. Results: The stool characteristics in the L, M and H groups were more severe than those in the NS and NM groups. Furthermore, the intestinal propulsion rate in the L, M and H groups was lower than that in the NS and NM groups. The C-kit mRNA and protein expression in the colon of rabbits were significantly lower in the L, M and H groups, when compared to the NS and NM groups. Conclusions: Naloxone blocked the mRNA and protein expression of C-kit, and improved intestinal motor function.

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