Substance P activates a non‐selective cation channel in murine pacemaker ICC

Abstract

Interstitial cells of Cajal (ICC) associated with Auerbach's plexus in the small intestine, provide pacemaker activity to orchestrate peristalsis and mixing. Despite the close apposition between ICC and enteric nerves, little is known about the neural regulation of pacemaker activity. The present study pursues the hypothesis that substance P can affect pacemaker activity through action on non-selective cation channels. Cell-attached and inside-out patch clamp studies were performed on isolated ICC in short-term cultures that provided evidence that substance P increases open probability or initiates activity in non-selective cation channels in ICC. The single-channel conductance is approximately 25 pS and in the on-cell configuration the activity can occur in a rhythmic fashion. Patches contained 1-10 channels and were most often accompanied by a approximately 12 pS chloride channel that was also activated by substance P. In a recently developed preparation that allows patch clamping in ICC in their natural environment within tissue, i.e. in situ, the presence of the channel and substance P activation was confirmed. The non-selective cation channel is one of the channels that initiate intestinal pacemaker activity and the present study provides further single-channel data on this critical channel. Because of the close proximity of enteric motor and sensory nerves to ICC, these data provide a potential mechanism underlying neural regulation of pacemaker activity. The data also indicate that neurokinergic pharmacology is a promising avenue for excitation of the intestinal pacemaker system.

AcMus: an open, integrated platform for room acoustics research

“…The simulation model implements geometrical acoustics and optimization techniques that allow the assessment of acoustical parameters of room designs and the solution of design problems, such as the optimal placement of sound sources and listeners, and optimal choices of geometry and surface materials to achieve desired acoustic properties, such as prescribed reverberation times for specific frequency ranges, or minimal harmonic distortion (used in the sense of timbral coloring, as in [7]). For spectral properties such as the latter it is desirable to obtain approximations of the frequency response of the room.…”

“…This is of particular importance for small rooms in which reflective surfaces are too close to the listener, thus making the reflected sound reach the listener immediately after the direct sound. To avoid extremely small values of the ITDG, recording studios use design concepts such as LEDE (Live End Dead End) [8] or RFZ (Reflection-Free Zone) [16]. In the LEDE concept half the room is designed to avoid primary reflections and the other half is designed to enhance diffusion.…”

“…RoomOptimizer [7] is a commercial package for the optimal placement of sound sources and listeners in a cuboid room. The problem is defined by trying to obtain the flattest frequency response possible, by trying many positions of sources and listeners and recalculating the impulse response.…”

“…Geometrical Acoustics: Two popular methods for the acoustical simulation of sound reflections based on geometrical models are ray-tracing and virtual image source [29,7,22].…”

“…Controlling these factors is essential to determine what we hear in situations such as concerts, recordings, electroacoustic music performances and listening to pre-recorded material. D'Antonio [7] indicates as critical factors "the quality of the electronics, the quality and placement of loudspeakers, the hearing ability and placement of the listener, the room dimensions (or geometry, if non-cuboid) and the acoustical condition of the room's boundary surfaces and contents. "…”