Lwc. Liu et Jd. Huizinga, CANINE COLONIC CIRCULAR MUSCLE GENERATES ACTION-POTENTIALS WITHOUT THE PACEMAKER COMPONENT, Canadian journal of physiology and pharmacology, 72(1), 1994, pp. 70-81
Two dominant types of action potentials in canine colon are slow wave
type action potentials (slow waves) and spike-like action potentials (
SLAPs). The slow waves, originating at the submuscular surface where a
network of interstitial cells of Cajal (ICCs) is found, possess a pac
emaker component. Activation of the pacemaker component is insensitive
to voltage changes and L-type calcium channel blockers, and is postul
ated to involve a metabolic clock sensitive to cyclic AMP. SLAPs are m
ore prominent in the longitudinal muscle. To understand the contributi
on circular muscle cells make to the generation of these action potent
ials, a circular muscle preparation (devoid of die submuscular ICC - s
mooth muscle network, longitudinal muscle, and myenteric plexus) was d
eveloped. Circular muscle preparations were spontaneously quiescent, w
ith a resting membrane potential of -62.9 +/- 0.6 mV. Ba2+ (0.5 mM) de
polarized the cells to 51.8 +/- 0.6 mV and induced electrical oscillat
ions with a frequency, duration, amplitude, and rate of rise equal to
6.6 +/- 0.4 cpm, 2.2 +/- 0.2 s, 19.4 +/- 0.9 mV, and 21.8 +/- 1.7 mV/s
, respectively. In most cases, Ba2+-induced oscillations were preceded
by a prepotential of 4.4 +/- 0.3 mV, with a rate of rise of 1.1 +/- 0
.1 mV/s. Ba2+-induced oscillations were abolished by 1 muM D600 as wel
l as by repolarization of 6-12 mV. Addition of 0.1 muM Bay K8644 in th
e presence of Ba2+ further depolarized circular muscle cells to -42.4
+/- 0.8 mV and increased the oscillation frequency to 16.8 +/- 1.8 cpm
. The electrical oscillations induced in circular muscle preparations
by Ba2+ and Bay K8644 were similar to the SLAPs exhibited by the isola
ted longitudinal muscle layer, indicating that generation of SLAPs is
an intrinsic property of smooth muscle cells. Forskolin (1 muM), previ
ously shown to dramatically decrease the frequency but not the amplitu
de of slow waves in preparations including the submuscular ICC network
, decreased the amplitude of the Ba2+-induced oscillations in circular
muscle preparations without changing the frequency. These results pro
vide strong evidence for the hypothesis that the submuscular ICC - smo
oth muscle network is essential for the initiation of the pacemaker co
mponent of the colonic slow waves. The mechanism for regulating the fr
equency of slow waves is different from that responsible for the Ba2+-
induced oscillations in circular muscle preparations. Circular muscle
cells are shown to be excitable and capable of generating oscillatory
activity dominated by L-type calcium channel activity, which is regula
ted by K+ conductance.