cAMP suppresses CA2+-dependent electrical activity of airway smooth muscle induced by TEA

1987 ◽  
Vol 62 (1) ◽  
pp. 175-179 ◽  
Author(s):  
I. S. Richards ◽  
J. Ousterhout ◽  
N. Sperelakis ◽  
C. G. Murlas
Keyword(s):  
Smooth Muscle ◽  
Electrical Activity ◽  
Airway Smooth Muscle ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Airway Smooth Muscle Cells ◽  
Cyclic Monophosphate ◽  
Spontaneous Action ◽  
Intracellular Microelectrodes ◽  
Spontaneous Action Potentials

Using intracellular microelectrodes, we investigated whether exogenous dibutyryl adenosine 3 ′,5′-cyclic monophosphate (DBcAMP) or forskolin influenced the electrical effects of tetraethylammonium (TEA) on canine tracheal smooth muscle. We found that 20 mM TEA depolarized airway smooth muscle cells from a resting membrane potential (Em) of -59 +/- 4 mV (mean +/- SD) to -45 +/- 2 mV and caused spontaneous action potentials (AP's) to develop, which were 33 +/- 2 mV in amplitude. These were totally abolished in 0 Ca2+ solution. DBcAMP (1 mM) suppressed the development of this TEA-induced electrical activity and the phasic contractions electrically coupled to it. DBcAMP had no significant effect on Em in the absence of TEA however. Forskolin (1 microM) produced similar effects. Our findings suggest that Ca2+ is the principal ion responsible for the inward current associated with the TEA-induced AP's in airway smooth muscle, and that adenosine 3′,5′-cyclic monophosphate may suppress the electrogenesis of this current.

Actions of histamine on muscle and ganglia of the guinea pig gallbladder

2000 ◽  
Vol 279 (3) ◽  
pp. G622-G630 ◽  
Author(s):  
Jason M. Hemming ◽  
Fay A. Guarraci ◽  
Tracy A. Firth ◽  
Lee J. Jennings ◽  
Mark T. Nelson ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mast Cells ◽  
Action Potentials ◽  
Resting Membrane Potential ◽  
Receptor Subtype ◽  
Excitatory Postsynaptic Potential ◽  
Membrane Hyperpolarization ◽  
Spontaneous Action ◽  
Induced Changes ◽  
Spontaneous Action Potentials

Histamine is an inflammatory mediator present in mast cells, which are abundant in the wall of the gallbladder. We examined the electrical properties of gallbladder smooth muscle and nerve associated with histamine-induced changes in gallbladder tone. Recordings were made from gallbladder smooth muscle and neurons, and responses to histamine and receptor subtype-specific compounds were tested. Histamine application to intact smooth muscle produced a concentration-dependent membrane depolarization and increased excitability. In the presence of the H2 antagonist ranitidine, the response to histamine was potentiated. Activation of H2 receptors caused membrane hyperpolarization and elimination of spontaneous action potentials. The H2response was attenuated by the ATP-sensitive K+(KATP) channel blocker glibenclamide in intact and isolated smooth muscle. Histamine had no effect on the resting membrane potential or excitability of gallbladder neurons. Furthermore, neither histamine nor the H3 agonist R-α-methylhistamine altered the amplitude of the fast excitatory postsynaptic potential in gallbladder ganglia. The mast cell degranulator compound 48/80 caused a smooth muscle depolarization that was inhibited by the H1 antagonist mepyramine, indicating that histamine released from mast cells can activate gallbladder smooth muscle. In conclusion, histamine released from mast cells can act on gallbladder smooth muscle, but not in ganglia. The depolarization and associated contraction of gallbladder smooth muscle represent the net effect of activation of both H1 (excitatory) and H2 (inhibitory) receptors, with the H2receptor-mediated response involving the activation of KATPchannels.

VIP inhibits basal and histamine-stimulated proliferation of human airway smooth muscle cells

1995 ◽  
Vol 268 (6) ◽  
pp. L1047-L1051 ◽  
Author(s):  
K. Maruno ◽  
A. Absood ◽  
S. I. Said
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Thymidine Incorporation ◽  
Inhibitory Effect ◽  
Airway Smooth Muscle Cells ◽  
Dependent Manner ◽  
Cyclic Monophosphate ◽  
Cell Counts ◽  
Dependent Protein ◽  
Camp Levels

Airway smooth muscle (ASM) cell proliferation contributes to increased airway resistance in bronchial asthma. We have examined the modulation of ASM proliferation by vasoactive intestinal peptide (VIP), a cotransmitter of airway relaxation. Human ASM cells were grown in culture as a monolayer. VIP (1.0 nM-1.0 microM) inhibited proliferation in a dose-dependent manner by up to 82% on day 2, but the related peptide glucagon had no effect. Histamine (100 nM-100 microM) increased cell counts by 66%, but in the presence of VIP, cell counts and [3H]thymidine incorporation were reduced by up to 55%. Adenosine 3',5'-cyclic monophosphate (cAMP)-promoting agents, including 3-isobutyl-1-methylxanthine, forskolin, and 8-bromo-adenosine 3',5'-cyclic monophosphate, alone and especially combined with VIP, reduced cell counts and [3H]thymidine incorporation, in correlation with cAMP levels. KT-5720 (1.0 nM-1.0 microM), a selective inhibitor of cAMP-dependent protein kinase A (PKA), abolished the inhibitory effect of VIP. The results show that VIP selectively and potently inhibits human ASM cell growth and multiplication, and nullifies the mitogenic effect of histamine, by a PKA-mediated mechanism. A deficiency of VIP may lead to ASM hyperplasia due to unopposed stimulation by endogenous mitogens.

Effects of cAMP on serotonin evoked calcium transients in cultured rat airway smooth muscle cells

1997 ◽  
Vol 272 (5) ◽  
pp. L865-L871 ◽  
Author(s):  
B. Tolloczko ◽  
Y. L. Jia ◽  
J. G. Martin
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Airway Smooth Muscle ◽  
Airway Smooth Muscle Cells ◽  
Intracellular Camp ◽  
Dependent Protein Kinase ◽  
Cyclic Monophosphate ◽  
Dependent Protein ◽  
High Concentrations

Agents increasing intracellular adenosine 3',5'-cyclic monophosphate (cAMP) cause relaxation of airway smooth muscle. However, the mechanisms of their action are not fully understood. We investigated the role of cAMP in the modulation of intracellular Ca2+ concentration ([Ca2+]i) transients evoked by serotonin (5-HT) in cultured rat tracheal smooth muscle (TSM) cells. Forskolin (10(-7) M) caused a significant elevation of intracellular cAMP and a 60% relaxation of tracheal rings contracted with 5-HT but did not affect [Ca2+]i in TSM cells. Forskolin (10(-5) M) completely relaxed tracheal rings and significantly decreased [Ca2+]i during the sustained phase of the 5-HT response. Forskolin-induced relaxation was attenuated by the cAMP-dependent protein kinase A (PKA) inhibitor Rp diastereomer of cAMP (Rp-cAMPS; 10(-4) M) and by the guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (PKG) inhibitor [Rp isomer of 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphorothioate, 10(-4) M]. The effects of forskolin on [Ca2+]i were not altered by the PKA inhibitor but were abolished by the PKG inhibitor and thapsigargin. These results indicate that, in rat TSM, the relaxant effects of high concentrations of cAMP may be mediated, at least in part, by facilitating the sequestration of Ca2+ into intracellular stores by a mechanism involving PKG.

scholarly journals Acidosis facilitates spontaneous sarcoplasmic reticulum Ca2+ release in rat myocardium.

1987 ◽  
Vol 90 (1) ◽  
pp. 145-165 ◽  
Author(s):  
C H Orchard ◽  
S R Houser ◽  
A A Kort ◽  
A Bahinski ◽  
M C Capogrossi ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Action Potentials ◽  
Laser Light ◽  
De Novo ◽  
Resting Membrane Potential ◽  
Resting Tension ◽  
Spontaneous Action ◽  
The Mean ◽  
Spontaneous Action Potentials ◽  
Tissue Motion

Previous studies have shown that acidosis increases myoplasmic [Ca2+] (Cai). We have investigated whether this facilitates spontaneous sarcoplasmic reticulum (SR) Ca2+ release and its functional sequelae. In unstimulated rat papillary muscles, exposure to an acid solution (produced by increasing the [CO2] of the perfusate from 5 to 20%) caused a rapid increase in the mean tissue Cai, as measured by the photoprotein aequorin. This was paralleled by an increase in spontaneous microscopic tissue motion caused by localized Ca2+ myofilament interactions, as monitored in fluctuations in the intensity of laser light scattered by the muscle. In regularly stimulated muscles, acidosis increased the size of the Ca2+ transient associated with each contraction and caused the appearance of Cai oscillations in the diastolic period. In unstimulated single myocytes, acidosis depolarized the resting membrane potential by approximately 5 mV and enhanced the frequency of spontaneous contractile waves. The small sarcolemmal depolarization associated with each contractile wave increased and occasionally initiated spontaneous action potentials. In regularly stimulated myocytes, acidosis caused de novo spontaneous contractile waves between twitches; these waves were associated with a decrease in the amplitude of the subsequent stimulated twitch. Ryanodine (2 microM) abolished all evidence of spontaneous Ca2+ release during acidosis, markedly reduced the acidosis-induced increase in aequorin light, and reduced resting tension. We conclude that acidosis increases the likelihood for the occurrence of spontaneous SR Ca2+ release, which can cause spontaneous action potentials, increase resting tension, and negatively affect twitch tension.

scholarly journals SK Current, Expressed During the Development and Regeneration of Chick Hair Cells, Contributes to the Patterning of Spontaneous Action Potentials

2022 ◽  
Vol 15 ◽  
Author(s):  
Snezana Levic
Keyword(s):  
Electrical Activity ◽  
Hair Cells ◽  
Action Potentials ◽  
Functional Expression ◽  
Basilar Papilla ◽  
Spontaneous Electrical Activity ◽  
Intracellular Ca ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Chick hair cells display calcium (Ca2+)-sensitive spontaneous action potentials during development and regeneration. The role of this activity is unclear but thought to be involved in establishing proper synaptic connections and tonotopic maps, both of which are instrumental to normal hearing. Using an electrophysiological approach, this work investigated the functional expression of Ca2+-sensitive potassium [IK(Ca)] currents and their role in spontaneous electrical activity in the developing and regenerating hair cells (HCs) in the chick basilar papilla. The main IK(Ca) in developing and regenerating chick HCs is an SK current, based on its sensitivity to apamin. Analysis of the functional expression of SK current showed that most dramatic changes occurred between E8 and E16. Specifically, there is a developmental downregulation of the SK current after E16. The SK current gating was very sensitive to the availability of intracellular Ca2+ but showed very little sensitivity to T-type voltage-gated Ca2+ channels, which are one of the hallmarks of developing and regenerating hair cells. Additionally, apamin reduced the frequency of spontaneous electrical activity in HCs, suggesting that SK current participates in patterning the spontaneous electrical activity of HCs.

PGE2 hyperpolarizes gallbladder neurons and inhibits synaptic potentials in gallbladder ganglia

1998 ◽  
Vol 274 (3) ◽  
pp. G493-G502 ◽  
Author(s):  
Lee J. Jennings ◽  
Gary M. Mawe
Keyword(s):  
Action Potentials ◽  
Input Resistance ◽  
Gallbladder Motility ◽  
Resting Membrane Potential ◽  
Prostaglandin E ◽  
Synaptic Potentials ◽  
Current Pulses ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials ◽  
Intramural Ganglia

Gallbladder prostaglandin E2(PGE2) levels are significantly elevated in pathophysiological conditions, resulting in changes in gallbladder motility or secretion that may involve actions of the prostanoid in intramural ganglia. This study was undertaken to examine the effects of PGE2 on neurons of the intramural ganglia of the guinea pig gallbladder. Application of PGE2 by microejection or superfusion elicited a complex triphasic change in the resting membrane potential (RMP). For example, application of PGE2 by microejection (100 μM) resulted in a brief hyperpolarization (mean duration 11.1 ± 1.3 s), followed by a mid-phase repolarization toward or above RMP (mean duration 50.7 ± 8.1 s), and finally a long-lasting hyperpolarization (mean duration 157.3 ± 36.7 s). Associated with these PGE2-evoked alterations in RMP were changes in input resistance measured via injection of hyperpolarizing current pulses. An examination of the action potential afterhyperpolarization (AHP) during the PGE2-evoked response revealed an attenuation of both the amplitude and duration of the AHP. However, only a slight increase in excitability of gallbladder neurons in the presence of PGE2 was evident in response to depolarizing current pulses, and PGE2 did not cause the cells to fire spontaneous action potentials. Application of PGE2 reduced the amplitudes of both fast and slow excitatory synaptic potentials. These results suggest that increased prostaglandin production may decrease ganglionic output and therefore contribute to gallbladder stasis.

scholarly journals Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses

Open Biology ◽  
2013 ◽  
Vol 3 (11) ◽  
pp. 130163 ◽  
Author(s):  
Stuart L. Johnson ◽  
Carolina Wedemeyer ◽  
Douglas E. Vetter ◽  
Roberto Adachi ◽  
Matthew C. Holley ◽  
...  
Keyword(s):  
Electrical Activity ◽  
Action Potentials ◽  
Cell Development ◽  
Sensory Cells ◽  
Inhibitory Input ◽  
Efferent System ◽  
Ribbon Synapses ◽  
Functional Maturation ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Spontaneous electrical activity generated by developing sensory cells and neurons is crucial for the maturation of neural circuits. The full maturation of mammalian auditory inner hair cells (IHCs) depends on patterns of spontaneous action potentials during a ‘critical period’ of development. The intrinsic spiking activity of IHCs can be modulated by inhibitory input from cholinergic efferent fibres descending from the brainstem, which transiently innervate immature IHCs. However, it remains unknown whether this transient efferent input to developing IHCs is required for their functional maturation. We used a mouse model that lacks the α9-nicotinic acetylcholine receptor subunit (α9nAChR) in IHCs and another lacking synaptotagmin-2 in the efferent terminals to remove or reduce efferent input to IHCs, respectively. We found that the efferent system is required for the developmental linearization of the Ca 2+ -sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their general cell development. This provides the first direct evidence that the efferent system, by modulating IHC electrical activity, is required for the maturation of the IHC synaptic machinery. The central control of sensory cell development is unique among sensory systems.

Pharmacological activation changes stiffness of cultured human airway smooth muscle cells

1996 ◽  
Vol 271 (5) ◽  
pp. C1660-C1668 ◽  
Author(s):  
R. D. Hubmayr ◽  
S. A. Shore ◽  
J. J. Fredberg ◽  
E. Planus ◽  
R. A. Panettieri ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
High Density ◽  
Cell Stiffness ◽  
Airway Smooth Muscle Cells ◽  
Human Airway Smooth Muscle ◽  
Cyclic Monophosphate ◽  
Human Airway

Using magnetic twisting cytometry (MTC), we measured the cytoskeletal stiffness of adherent human airway smooth muscle (HASM) cells. We hypothesized that modulation of actin-myosin interactions by application of contractile agonists would induce changes in cytoskeletal stiffness. In cells plated on high-density collagen, bradykinin (10(-6) M) and histamine (10(-4) M) increased stiffness by 85 +/- 15 and 68 +/- 16%, respectively. Increases in cell stiffness were also consistently observed after acetylcholine, substance P, and KCl. The bronchodilator agonists isoproterenol, prostaglandin E2, forskolin, dibutryl adenosine 3', 5'-cyclic monophosphate, and 8-bromoguanosine 3', 5'-cyclic monophosphate each caused a dose-dependent decrease in cell stiffness in unstimulated as well as bradykinin-treated cells. HASM cells plated on high-density collagen were stiffer than cells plated on low-density collagen (126 +/- 16 vs. 43 +/- 3 dyn/cm2) and developed more pronounced increases in stiffness in response to bradykinin as well as more pronounced decreases in stiffness in response to isoproterenol. These results are consistent with the hypothesis that modulation of actin-myosin interactions by application of contractile agonists causes changes in cytoskeletal stiffness of HASM cells. MTC may be a valuable tool for evaluating the mechanisms of pharmacomechanical coupling in airway smooth muscle cells in culture.

Cholesterol inhibits spontaneous action potentials and calcium currents in guinea pig gallbladder smooth muscle

1999 ◽  
Vol 277 (5) ◽  
pp. G1017-G1026 ◽  
Author(s):  
Lee J. Jennings ◽  
Qi-Wei Xu ◽  
Tracy A. Firth ◽  
Mark T. Nelson ◽  
Gary M. Mawe
Keyword(s):  
Smooth Muscle ◽  
Action Potentials ◽  
Second Messenger ◽  
Calcium Currents ◽  
Isolated Cells ◽  
Receptor Ligand ◽  
Intact Tissue ◽  
Elevated Cholesterol ◽  
Spontaneous Action ◽  
Spontaneous Action Potentials

Elevated cholesterol decreases agonist-induced contractility and enhances stone formation in the gallbladder. The current study was conducted to determine if and how the electrical properties and ionic conductances of gallbladder smooth muscle are altered by elevated cholesterol. Cholesterol was delivered as a complex with cyclodextrin, and effects were evaluated with intracellular recordings from intact gallbladder and whole cell patch-clamp recordings from isolated cells. Cholesterol significantly attenuated the spontaneous action potentials of intact tissue. Furthermore, calcium-dependent action potentials and calcium currents were reduced in the intact tissue and in isolated cells, respectively. However, neither membrane potential hyperpolarizations induced by the ATP-sensitive potassium channel opener, pinacidil, nor voltage-activated outward potassium currents were affected by cholesterol. Hyperpolarizations elicited by calcitonin gene-related peptide were reduced by cholesterol enrichment, indicating potential changes in receptor ligand binding and/or second messenger interactions. These data indicate that excess cholesterol can contribute to gallbladder stasis by affecting calcium channel activity, whereas potassium channels remained unaffected. In addition, cholesterol enrichment may also modulate receptor ligand behavior and/or second messenger interactions.

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