Loss of responsiveness of circular smooth muscle cells from the guinea pig ileum is associated with changes in gap junction coupling

2012 ◽  
Vol 302 (12) ◽  
pp. G1434-G1444 ◽  
Author(s):  
Simona E. Carbone ◽  
David A. Wattchow ◽  
Nick J. Spencer ◽  
Simon J. H. Brookes
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Gap Junction ◽  
Input Resistance ◽  
Muscle Cells ◽  
Dye Coupling ◽  
Circular Smooth Muscle ◽  
Gap Junction Coupling ◽  
Excitatory Junction Potentials ◽  
Junction Coupling

Gap junction coupling and neuromuscular transmission to smooth muscle were studied in the first 4 h after preparations were set up in vitro. Intracellular recordings were made from smooth muscle cells of guinea pig ileum. Fast inhibitory junction potentials (IJPs) were small (1.3 ± 1.0 mV) in the first 30 min but increased significantly over the first 120 min to 15.8 ± 0.9 mV ( n = 12, P < 0.001). Comparable increases in slow IJPs and excitatory junction potentials were also observed. During the same period, resting membrane potential depolarized from −58.8 ± 1.4 to −47.2 ± 0.4 mV ( n = 12, P < 0.001). Input resistance, estimated by intracellular current injection, decreased in parallel ( P < 0.05), and dye coupling, measured by intracellular injection of carboxyfluorescein, increased ( P < 0.001). Input resistance was higher and dye coupling was less in longitudinal than circular smooth muscle cells. Gap junction blockers [carbenoxolone (100 μM), 18β-glycyrrhetinic acid (10 μM), and 2-aminoethoxydiphenyl borate (50 μM)] hyperpolarized coupled circular smooth muscle cells, reduced the amplitude of fast and slow IJPs and excitatory junction potentials, increased input resistance, and reduced dye coupling. Local application of ATP (10 mM) mimicked IJPs and showed comparable increases in amplitude over the first 120 min; carbenoxolone and 2-aminoethoxydiphenyl borate significantly reduced ATP-evoked hyperpolarizations in coupled cells. In contrast, synaptic transmission between myenteric neurons was not suppressed during the first 30 min. Gap junction coupling between circular smooth muscle cells in isolated preparations was initially disrupted but recovered over the next 120 min to a steady level. This was associated with potent effects on neuromuscular transmission and responses to exogenous ATP.

NUMERICAL SIMULATION OF THE ROLE OF CO-TRANSMISSION BY ACETYLCHOLINE AND SEROTONIN ON MOTILITY OF THE GUT

2006 ◽  
Vol 06 (04) ◽  
pp. 399-428
Author(s):  
R. MIFTAHOF
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Transit Time ◽  
Receptor Agonist ◽  
Muscle Cells ◽  
Receptor Antagonists ◽  
One Dimensional ◽  
Circular Smooth Muscle ◽  
Spatio Temporal ◽  
Stimulation Of

Electrophysiological mechanisms of co-transmission by serotonin (5-HT) and acetylcholine (ACh), co-expression of their receptor types, i.e., 5-HT type 3 and 4, nicotinic cholinerginc (nACh) and muscarinic cholinergic (μACh), and effects of selective and non-selective 5-HT3 and 5-HT4 receptor agonists/antagonists, on electromechanical activity of the gut were studied numerically. Two series of numerical experiments were performed. First, the dynamics of the generation and propagation of electrical signals interconnected with the primary sensory (AH) neurons, motor (S) neurons and smooth muscle cells were studied in a one-dimensional model. Simulations showed that stimulation of the 5-HT3 receptors reduced the threshold of activation of the mechanoreceptors by 17.6%. Conjoint excitation of the 5-HT3 and 5-HT4 receptors by endogenous serotonin converted the regular firing pattern of electrical discharges of the AH and S neurons to a beating mode. Activation confined to 5-HT3 receptors, located on the somas of the adjacent AH and S type neurons, could not sustain normal signal transduction between them. It required ACh as a co-transmitter and co-activation of the nACh receptors. Application of selective 5-HT3 receptor antagonists inhibited dose-dependently the production of action potentials at the level of mechanoreceptors and the soma of the primary sensory neuron and increased the threshold activation of the mechanoreceptors. Normal mechanical contractile activity depended on co-stimulation of the 5-HT4 and μACh receptors on the membrane of smooth muscle cells. In the second series of simulations, which involved a spatio-temporal model of the functional unit, effects of co-transmission by ACh and 5-HT on the electromechanical response in a segment of the gut were analyzed. Results indicated that propagation of the wave of excitation between the AH and S neurons within the myenteric nervous plexus in the presence of 5-HT3 receptor antagonists was supported by co-release of ACh. Co-stimulation of 5-HT3, nACh and μACh receptors impaired propulsive activity of the gut. The bolus showed uncoordinated movements. In an ACh-free environment Lotronex (GlaxoSmithKline), a 5-HT3 receptor antagonist, significantly increased the transit time of the pellet along the gut. In the presence of ACh, Lotronex produced intensive tonic-type contractions in the longitudinal and circular smooth muscle layers and eliminated propulsive activity. The 5HT4 receptor agonist, Zelnorm (Novartis), preserved the reciprocal electromechanical relationships between the longitudinal and circular smooth muscle layers. The drug changed the normal propulsive pattern of activity to an expulsive (non-mixing) type. Treatment of the gut with selective 5HT4 receptor antagonists increased the transit time by disrupting the migrating myoelectrical complex. Cisapride (Janssen), a mixed 5HT3 and 5HT4 receptor agonist, increased excitability of the AH and S neurons and the frequency of slow waves. Longitudinal and circular smooth muscle syncytia responded with the generation of long-lasting tonic contractions, resulting in a "squeezing" type of pellet movement. Comparison of the theoretical results obtained on one-dimensional and spatio-temporal models to in vivo and in vitro experimental data indicated satisfactory qualitative, and where available, quantitative agreement.

SCN5A is expressed in human jejunal circular smooth muscle cells

2002 ◽  
Vol 14 (5) ◽  
pp. 477-486 ◽  
Author(s):  
Y. Ou ◽  
S. J. Gibbons ◽  
S. M. Miller ◽  
P. R. Strege ◽  
A. Rich ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Circular Smooth Muscle

Beta-adrenergic actions on membrane electrical properties of dissociated smooth muscle cells

1988 ◽  
Vol 254 (3) ◽  
pp. C423-C431 ◽  
Author(s):  
H. Yamaguchi ◽  
T. W. Honeyman ◽  
F. S. Fay
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Electrical Properties ◽  
Smooth Muscle Cells ◽  
Input Resistance ◽  
Muscle Cells ◽  
Resting Potential ◽  
Equilibrium Potential ◽  
Dependent Manner ◽  
Beta Adrenergic

Studies were carried out to determine the effects of the beta-adrenergic agent, isoproterenol (ISO), on membrane electrical properties in single smooth muscle cells enzymatically dispersed from toad stomach. In cells bathed in buffer of physiological composition, the average resting potential was -56.4 +/- 1.4 mV (mean +/- SE, n = 35). The dominant effect of exposure to ISO was hyperpolarization. The hyperpolarization was apparent in all cells studied and averaged 11.6 +/- 1.2 mV (n = 27). In the majority of the cells, hyperpolarization was accompanied by a decreased input resistance (Rin). Often the change in resistance appeared to lag behind the change in membrane potential. The lack of coincident changes in membrane potential and resistance may reflect a superposition of the outward rectification properties of the membrane on beta-adrenergic-induced increases in ionic conductance. In about half of the cells, an initial small depolarization (3.1 +/- 0.3 mV, n = 14) was accompanied by a small but distinct increase in Rin (12 +/- 2.5%). When membrane potential was made more negative than the estimated equilibrium potential for K+ (EK) by injection of current, ISO also produced biphasic effects, an initial hyperpolarization which reversed to a sustained depolarization to a value (-90 mV) near the estimated EK. The hyperpolarization by ISO could be diminished in a time-dependent manner by previous exposure to ouabain. The inhibition by ouabain, however, appeared to be a fortuitous result of glycoside-induced positive shifts in EK. These observations indicate that the dominant electrophysiological effect of beta-adrenergic stimuli is to hyperpolarize the cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of HERG-like K+ currents in opossum esophageal circular smooth muscle

1999 ◽  
Vol 277 (6) ◽  
pp. C1284-C1290 ◽  
Author(s):  
Hamid I. Akbarali ◽  
Hemant Thatte ◽  
Xue Dao He ◽  
Wayne R. Giles ◽  
Raj K. Goyal
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Single Cells ◽  
Circular Muscle ◽  
Muscle Cells ◽  
Resting Membrane Potential ◽  
Channel Blockers ◽  
Circular Smooth Muscle ◽  
Inward Currents

An inwardly rectifying K+ conductance closely resembling the human ether-a-go-go-related gene (HERG) current was identified in single smooth muscle cells of opossum esophageal circular muscle. When cells were voltage clamped at 0 mV, in isotonic K+ solution (140 mM), step hyperpolarizations to −120 mV in 10-mV increments resulted in large inward currents that activated rapidly and then declined slowly (inactivated) during the test pulse in a time- and voltage- dependent fashion. The HERG K+ channel blockers E-4031 (1 μM), cisapride (1 μM), and La3+ (100 μM) strongly inhibited these currents as did millimolar concentrations of Ba2+. Immunoflourescence staining with anti-HERG antibody in single cells resulted in punctate staining at the sarcolemma. At membrane potentials near the resting membrane potential (−50 to −70 mV), this K+ conductance did not inactivate completely. In conventional microelectrode recordings, both E-4031 and cisapride depolarized tissue strips by 10 mV and also induced phasic contractions. In combination, these results provide direct experimental evidence for expression of HERG-like K+ currents in gastrointestinal smooth muscle cells and suggest that HERG plays an important role in modulating the resting membrane potential.

Effect of platelet-derived growth factor-BB on gap junction and connexin43 in rat penile corpus cavernosum smooth muscle cells

Andrologia ◽  
2018 ◽  
Vol 51 (3) ◽  
pp. e13200 ◽  
Author(s):  
Fan Zhao ◽  
Junfeng Yan ◽  
Jianfeng Zhao ◽  
Bing Shi ◽  
Miaoyong Ye ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Gap Junction ◽  
Corpus Cavernosum ◽  
Muscle Cells ◽  
Platelet Derived Growth Factor
Sign in / Sign up

Export Citation Format

Share Document