III. The mechanisms of action of neurotransmitters - Electrical changes underlying excitation and inhibition in intestinal and related smooth muscle

1973 ◽  
Vol 265 (867) ◽  
pp. 95-106 ◽  
Keyword(s):  
Smooth Muscle ◽  
Adrenergic Innervation ◽  
Resting Potential ◽  
Adrenergic Nerve ◽  
Field Stimulation ◽  
Low Frequencies ◽  
Single Spike ◽  
The Mean ◽  
Membrane Oscillations ◽  
Resting Tone

Intestinal smooth muscle is normally spontaneously active and contraction is associated with spike activity. Stimulation of excitatory (cholinergic) nerves increases spike frequency while inhibitory (adrenergic) nerve activity reduces slow waves and spikes without necessarily producing hyperpolarization. Activity of intrinsic nerves produces inhibition with marked hyperpolarization. The anococcygeus muscle of the rat, a muscle associated with the alimentary canal, has a dense adrenergic innervation and has neither resting tone nor spontaneous activity. The mean resting potential is 58.4 mV. Field stimulation produces graded depolarization associated with contraction and abolished by phentolamine. The depolarization has an initial component of up to 10 mV followed by a response which can reach 50 mV, the largest sometimes having a single spike on the rising phase. Application of noradrenaline or guanethidine produces depolarization with oscillations at 1/s and maintained contraction. Field stimulation at low frequencies during this contraction causes relaxation and reduction in the membrane oscillations but no repolarization.

Studies of the innervation of rabbit myometrium and cervix

1989 ◽  
Vol 67 (8) ◽  
pp. 837-844 ◽  
Author(s):  
R. Bulat ◽  
M. S. Kannan ◽  
R. E. Garfield
Keyword(s):  
Electron Microscopy ◽  
Smooth Muscle ◽  
Blood Vessels ◽  
Spontaneous Activity ◽  
Isometric Contraction ◽  
Glyoxylic Acid ◽  
Adrenergic Innervation ◽  
Significant Inhibition ◽  
Adrenergic Nerves ◽  
Field Stimulation

We characterized the innervation of isolated circular and longitudinal-oriented muscle strips from the nulliparous rabbit uterus and cervix by field stimulation (FS). FS with increasing frequency (2.5–50 pps) and voltage (2.5–70 V) caused graded increases in isometric contraction with no relaxation or inhibition of spontaneous activity. Tetrodotoxin(TTX, 3.1 × 10−6 M) significantly reduced the FS response by 75% in all strips at higher stimulus frequencies. Contractile responses to FS were also significantly inhibited by atropine (3.5 × 10−6 M) in circular uterus and in longitudinal cervix. Guanethidine (5 × 10−6 M) reduced the response in all strips, as did phentolamine (3.6 × 10−6 M) in longitudinal uterus and circular cervix. Propranolol (3.9 × 10−6 M) did not significantly change the response in longitudinal uterus or circular cervix. In longitudinal uterus, combined guanethidine and atropine produced significant inhibition, but not statistically different from either drug alone. Similar results were seen in circular uterus. Electron microscopy and glyoxylic acid histofluorescence indicate that both blood vessels and smooth muscle in rabbit uterus are supplied with adrenergic nerves. The results suggest the presence of TTX-sensitive adrenergic and cholinergic excitatory innervation of rabbit uterus and cervix.Key words: uterus, myometrium, cervix, adrenergic innervation.

The innervation of smooth muscle in the primary bronchus of the chicken

1980 ◽  
Vol 58 (3) ◽  
pp. 310-315 ◽  
Author(s):  
R. Bhatla ◽  
C. C. Ferguson ◽  
J. B. Richardson
Keyword(s):  
Smooth Muscle ◽  
Adrenergic Innervation ◽  
Primary Response ◽  
Cholinergic Innervation ◽  
Field Stimulation ◽  
Inhibitory System ◽  
Granular Vesicles ◽  
Adrenergic Blocking ◽  
Large Granular Vesicles

The innervation of the primary bronchus of the chicken was studied with in vitro pharmacological techniques and with the electron microscope. The primary response of the smooth muscle to field stimulation is relaxation of the muscle and this is not blocked by adrenergic blocking agents. Excitatory cholinergic innervation can be demonstrated when the muscle is partially relaxed. Examination of the ultrastructure of the muscle and nerves shows numerous axon profiles filled with large granular vesicles of the type associated with noradrenergic or purinergic neurotransmission. Agranular vesicles characteristic of cholinergic innervation are also seen but there is no evidence of adrenergic innervation to the smooth muscle. The smooth muscle ceils show connections of the nexus type. These findings indicate that the primary bronchus of the chicken has a dominant inhibitory system and this is nonadrenergic in type.

scholarly journals The Contraction of Smooth Muscle Cells of Intrapulmonary Arterioles Is Determined by the Frequency of Ca2+ Oscillations Induced by 5-HT and KCl

2005 ◽  
Vol 125 (6) ◽  
pp. 555-567 ◽  
Author(s):  
Jose F. Perez ◽  
Michael J. Sanderson
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Confocal Microscopy ◽  
Smooth Muscle Cells ◽  
Phase Contrast ◽  
Muscle Cells ◽  
Low Frequencies ◽  
Scanning Confocal Microscopy ◽  
Agonist Concentration ◽  
Mouse Lungs

Increased resistance of the small blood vessels within the lungs is associated with pulmonary hypertension and results from a decrease in size induced by the contraction of their smooth muscle cells (SMCs). To study the mechanisms that regulate the contraction of intrapulmonary arteriole SMCs, the contractile and Ca2+ responses of the arteriole SMCs to 5-hydroxytrypamine (5-HT) and KCl were observed with phase-contrast and scanning confocal microscopy in thin lung slices cut from mouse lungs stiffened with agarose and gelatin. 5-HT induced a concentration-dependent contraction of the arterioles. Increasing concentrations of extracellular KCl induced transient contractions in the SMCs and a reduction in the arteriole luminal size. 5-HT induced oscillations in [Ca2+]i within the SMCs, and the frequency of these Ca2+ oscillations was dependent on the agonist concentration and correlated with the extent of sustained arteriole contraction. By contrast, KCl induced Ca2+ oscillations that occurred with low frequencies and were preceded by small, localized transient Ca2+ events. The 5-HT–induced Ca2+ oscillations and contractions occurred in the absence of extracellular Ca2+ and were resistant to Ni2+ and nifedipine but were abolished by caffeine. KCl-induced Ca2+ oscillations and contractions were abolished by the absence of extracellular Ca2+ and the presence of Ni2+, nifedipine, and caffeine. Arteriole contraction was induced or abolished by a 5-HT2–specific agonist or antagonist, respectively. These results indicate that 5-HT, acting via 5-HT2 receptors, induces arteriole contraction by initiating Ca2+ oscillations and that KCl induces contraction via Ca2+ transients resulting from the overfilling of internal Ca2+ stores. We hypothesize that the magnitude of the sustained intrapulmonary SMC contraction is determined by the frequency of Ca2+ oscillations and also by the relaxation rate of the SMC.

scholarly journals Electron microscopy of synthetic myosin filaments. Evidence for cross-bridge. Flexibility and copolymer formation.

1975 ◽  
Vol 67 (1) ◽  
pp. 93-104 ◽  
Author(s):  
T D Pollard
Keyword(s):  
Skeletal Muscle ◽  
Smooth Muscle ◽  
Structural Features ◽  
Length Frequency ◽  
Single Population ◽  
Skeletal Muscle Myosin ◽  
Distinctive Features ◽  
Myosin Filaments ◽  
The Mean ◽  
Muscle Myosin

Electron micrographs of negatively stained synthetic myosin filaments reveal that surface projections, believed to be the heads of the constituent myosin molecules, can exist in two configurations. Some filaments have the projections disposed close to the filament backbone. Other filaments have all of their projections widely spread, tethered to the backbone by slender threads. Filaments formed from the myosins of skeletal muscle, smooth muscle, and platelets each have distinctive features, particularly their lengths. Soluble mixtures of skeletal muscle myosin with either smooth muscle myosin or platelet myosin were dialyzed against 0.1 M KC1 at pH 7 to determine whether the simultaneous presence of two types of myosin would influence the properties of the filaments formed. In every case, a single population of filaments formed from the mixtures. The resulting filaments are thought to be copolymers of the two types of myosin, for several reasons: (a) their length-frequency distribution is unimodal and differs from that predicted for a simple mixture of two types of myosin filaments; (b) their mean length is intermediate between the mean lengths of the filaments formed separately from the two myosins in the mixture; (c) each of the filaments has structural features characteristic of both of the myosins in the mixture; and (d) their size and shape are determined by the proportion of the two myosins in the mixture.

CHANGES IN THE RESTING POTENTIAL OF SKELETAL MUSCLE IN RATS WITH COLD ACCLIMATION

1966 ◽  
Vol 44 (5) ◽  
pp. 791-802 ◽  
Author(s):  
M. H. Sherebrin ◽  
A. C. Burton
Keyword(s):  
Skeletal Muscle ◽  
Electrical Properties ◽  
Cold Acclimation ◽  
White Muscle ◽  
Single Cells ◽  
Temperature Gradients ◽  
Resting Potential ◽  
The Mean ◽  
Shivering Thermogenesis ◽  
Main Factor

The resting potential of single cells in the flexor thigh muscles of rats was measured in an attempt to find a change in the electrical properties of the cell membrane with cold acclimation, in order to identify and relate metabolic changes occurring with non-shivering thermogenesis. The mean resting potential of cells in cold-acclimated rats was found to be slightly but significantly higher than in the controls. A larger temperature gradient with depth was measured in the cold-acclimated animals than in the controls. If the Q10 of resting potential with temperature is as great as 1.16, the higher potential in the cold-acclimated rats may be accounted for by this temperature difference. The resting potential was also found to vary with depth in both groups of rats. This could not be attributed to temperature gradients, and change from red to white muscle cells with depth is thought to be the main factor for the increase of potential with depth.

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)

scholarly journals Parathyroid Hormone-Related Protein in Rat Penis: Expression, Localization, and Effect on Cavernosal Pressure1

Endocrinology ◽  
1999 ◽  
Vol 140 (9) ◽  
pp. 4342-4350 ◽  
Author(s):  
Hervé Lang ◽  
Nicole Endlich ◽  
Véronique Lindner ◽  
Karlhans Endlich ◽  
Thierry Massfelder ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Messenger Rna ◽  
Corpus Cavernosa ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Dilatory Response ◽  
Dorsal Nerve ◽  
The Mean ◽  
Immunohistochemical Studies ◽  
Functional Components

Abstract Although PTH-related protein-(1–36) [PTHrP-(1–36)] is known to be expressed in smooth muscle and to exert potent myorelaxant effects, its tonic effects on cavernosal smooth muscle has not yet been explored. Using the RT-PCR technique, the present study establishes that PTHrP messenger RNA is present in microdissected corpus cavernosa in the rat. In immunohistochemical studies using affinity-purified antibodies to middle regions of PTHrP, immunostaining was localized throughout the penile structures, including vessels, cavernosal smooth muscle, and trabecular fibroblasts. Strong immunostaining for PTHrP was also detected in the dorsal nerve bundles. In anesthetized rats, intracavernosally injected boluses of increasing doses of PTHrP-(1–36) (0.3–30 pmol in 100 μl saline) had little effect on intracavernosal pressure. However, they markedly potentiated the dilatory response to papaverine (8–800 nmol), increasing the papaverine-induced intracavernous pressure by 2.5-fold, close to the mean arterial pressure. In conclusion, the cavernosal expression of PTHrP messenger RNA, the distribution of immunoreactive PTHrP throughout the structuro-functional components of the erectile apparatus and its strong potentiating action on papaverine-induced cavernosal relaxation, collectively suggest that PTHrP participates in the control of cavernosal tone.

scholarly journals Adrenergic airway vascular smooth muscle responsiveness in healthy and asthmatic subjects

2001 ◽  
Vol 90 (2) ◽  
pp. 665-669 ◽  
Author(s):  
Jorge Brieva ◽  
Adam Wanner
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Dead Space ◽  
Healthy Subjects ◽  
Contractile Response ◽  
Mucosal Blood Flow ◽  
Forced Expiratory Volume ◽  
Baseline Values ◽  
The Mean

The purpose of the present study was to determine the responsiveness of airway vascular smooth muscle (AVSM) as assessed by airway mucosal blood flow (Q˙aw) to inhaled methoxamine (α1-agonist; 0.6–2.3 mg) and albuterol (β2-agonist; 0.2–1.2 mg) in healthy [ n = 11; forced expiratory volume in 1 s, 92 ± 4 (SE) % of predicted] and asthmatic ( n = 11, mean forced expiratory volume in 1 s, 81 ± 5%) adults. Mean baseline values for Q˙aw were 43.8 ± 0.7 and 54.3 ± 0.8 μl · min−1· ml−1of anatomic dead space in healthy and asthmatic subjects, respectively ( P < 0.05). After methoxamine inhalation, the maximal mean change in Q˙aw was −13.5 ± 1.0 μl · min−1· ml−1in asthmatic and −7.1 ± 2.1 μl · min−1· ml−1in healthy subjects ( P < 0.05). After albuterol, the mean maximal change in Q˙aw was 3.0 ± 0.8 μl · min−1· ml−1in asthmatic and 14.0 ± 1.1 μl · min−1· ml−1in healthy subjects ( P < 0.05). These results demonstrate that the contractile response of AVSM to α1-adrenoceptor activation is enhanced and the dilator response of AVSM to β2-adrenoceptor activation is blunted in asthmatic subjects.

Interplay of VIP and nitric oxide in regulation of the descending relaxation phase of peristalsis

1993 ◽  
Vol 264 (2) ◽  
pp. G334-G340 ◽  
Author(s):  
J. R. Grider
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Protein Kinase G ◽  
Rat Colon ◽  
No Production ◽  
Field Stimulation ◽  
Relaxant Effect ◽  
Relaxation Phase ◽  
Kinase A

Involvement of vasoactive intestinal peptide (VIP) and nitric oxide (NO) in neurally induced relaxation was examined in smooth muscle from rat colon. Relaxation induced by field stimulation or radial stretch (i.e., descending relaxation phase of the peristaltic reflex) was accompanied by VIP release and NO production. NG-nitro-L-arginine (L-NNA) abolished NO production in both preparations but only partly inhibited VIP release (45 +/- 8% at 8 Hz and 59 +/- 10% at 10 g stretch) and relaxation (62 +/- 5% and 35 +/- 6%); the effect of L-NNA was reversed by L-arginine but not D-arginine. The pattern implied that NO production normally acts to enhance VIP release. In addition, VIP induced relaxation and stimulated NO production in muscle strips and isolated colonic muscle cells: L-NNA abolished NO production but only partly inhibited relaxation (58 +/- 6%); oxyhemoglobin had no effect. The effect of L-NNA on relaxation was reversed by L-arginine but not by D-arginine. The protein kinase A inhibitor (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS] and the protein kinase G inhibitor KT5823 inhibited VIP-induced relaxation by 76 +/- 5 and 35 +/- 4%, respectively; a combination of the two inhibitors abolished relaxation. (R)-p-cAMPS blocked the direct relaxant effect of VIP, whereas KT5823 blocked the indirect effect of VIP mediated by NO.(ABSTRACT TRUNCATED AT 250 WORDS)

Degeneration and Regrowth of Adrenergic Nerve Fibers in the Rat Peripheral Tissues after 6-Hydroxydopamine

1971 ◽  
Vol 49 (4) ◽  
pp. 345-355 ◽  
Author(s):  
J. de Champlain
Keyword(s):  
Ganglion Cells ◽  
Adrenergic Innervation ◽  
Nerve Fibers ◽  
Adrenergic Nerve ◽  
High Dose ◽  
Rat Tissues ◽  
Peripheral Tissues ◽  
Endogenous Noradrenaline ◽  
6 Hydroxydopamine ◽  
Noradrenaline Levels

Histofluorescent and biochemical changes in the adrenergic nervous system were followed up in rat tissues after one single intravenous injection of a high dose of 100 mg/kg of 6-hydroxydopamine (6-OH-DA). This treatment results in the rapid disappearance of terminal and preterminal fibers in the iris, atria, and small arteries of rats, whereas endogenous noradrenaline pools of the heart are 95% depleted. The capacity of the adrenergic nerve to take up and accumulate tritiated noradrenaline is reduced proportionally to the reduction in endogenous noradrenaline levels. These changes are compatible with the concept of a complete sympathectomy induced by the specific toxic action of 6-OH-DA on the adrenergic fibers. This sympathectomy is not permanent, however, and numerous bundles of preterminal fibers start to grow in the iris and atria within 4 to 5 days following injection. Progressively, in the following weeks, these fibers distribute over the whole organ and give birth to terminal fibers which form a new adrenergic plexus in these tissues. A completely normal innervation is restored 2 to 3 months after administration of 6-OH-DA. The endogenous noradrenaline levels rise progressively in parallel to the development of the new plexus of fibers. Since a complete regeneration of the adrenergic innervation can be demonstrated in the weeks following injection of 6-OH-DA, it appears that this compound can selectively destroy the adrenergic terminal and preterminal fibers without causing a degeneration of the adrenergic ganglion cells.

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