Nitrergic signaling via interstitial cells of Cajal and smooth muscle cells influences circular smooth muscle contractility in murine colon

Abstract

We conclude that short rings of murine colon can be effectively used to record spontaneous contractions. Although NO-GC in SMC determines smooth muscle tone, concerted action of NO-GC in both SMC and ICC modulates slow phasic contractions and large contractions.

Cell‐specific effects of nitric oxide on the efficiency and frequency of long distance contractions in murine colon

“…LDCs are composed of an initial relaxation phase followed by the propagating contraction (see Figure A‐1); (2) slow phasic contractions which are generated in both the longitudinal and circular muscle layer, thus, appear as V‐shaped oscillations in the spatiotemporal maps due to longitudinal muscle movement (see Figure A‐2); (3) continuous high‐frequency ripples (see Figure A‐3). As previously reported, all three types of contraction can also be recorded with colonic rings in a myography setup (Figure B) …”

“…Comparison of WT animals with the controls used for the cell‐specific KOs (which receive normal rodent chow) did not show any differences in colonic motility; thus, data were combined and indicated as WT. The efficacy of NO‐GC deletion in the SMC‐ and ICC‐GCKO has been shown previously . Animals of either sex were sacrificed at an age of 8‐16 weeks by cervical dislocation, and colons were isolated.…”

“…Guanylyl cyclase knockout animals and cell‐specific knockout mice for ICC, SMC, and SMC/ICC were generated according to Friebe et al and Beck et al WT siblings were used as controls for GCKO animals (both receiving the same diet). Heterozygous (+/flox) animals were used as controls for cell‐specific KOs (either flox/flox or −/flox); both carried the respective Cre gene and were treated with tamoxifen.…”

“…Our previous studies using colonic ring preparations provided evidence for an NO‐dependent regulation of murine colon contractility: Whereas ripples occur independent of NO, NO‐GC in both ICC and SMC is involved in the modulation of slow phasic contractions as well as large neurogenic contractions of colon rings. However, as our previous study evaluated the contractility of small colon rings, the analysis of propagating contractions was not possible. Thus, the present study focuses on the evaluation of NO‐GC signaling in preparations of whole colon to allow comparison to the data obtained with colon rings.…”

“…ICC‐SMP generate slow waves to initiate high‐frequency ripples in the circular muscle layer, whereas ICC‐MP likely generate the slow phasic contractions in both circular and longitudinal muscle layers . Both types of contraction occur in the presence of neuronal blockers such as tetrodotoxin (TTX) or hexamethonium indicating their myogenic origin …”