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

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.

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Facial Nerve Schwannomas Mimicking as Vestibular Schwannomas

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0037-1598636 ◽

2017 ◽

Vol 78 (04) ◽

pp. 283-287

Author(s):

Sean Wise ◽

David Cohen ◽

Jason Bell ◽

Dennis Bojrab ◽

Michael LaRouere ◽

...

Keyword(s):

Facial Nerve ◽

Outcome Measures ◽

Action Potentials ◽

Internal Auditory Canal ◽

Vestibular Schwannomas ◽

Tumor Capsule ◽

Spontaneous Action ◽

The Mean ◽

Spontaneous Action Potentials ◽

Stimulation Of

Objective The objective of this study was to identify preoperative and intraoperative findings that may aid in distinguishing facial nerve schwannomas (FNS) from vestibular schwannomas (VSs), particularly in cases limited to the internal auditory canal (IAC) and cerebellopontine angle (CPA). Study Design This was a retrospective study. Setting This study was set at a Tertiary Referral Center. Patients Seventeen cases from October 2002 to July 2015 with an IAC/CPA mass presumed to be a VS who were found to have a FNS intraoperatively. Main Outcome Measures The main outcome measures included preoperative presentation, intraoperative findings, and subsequent intervention. Results Preoperative hearing loss and imbalance were seen in 70.5 and 64.7%, respectively. Suspicious intraoperative findings included: facial nerve incorporated intimately with the tumor capsule in 12 cases; spontaneous action potentials noted while drilling the bony IAC in 3 cases; and action potentials noted on stimulation of the entire tumor capsule in 10 cases. The mean long-term facial function was House–Brackmann grade II and the mean length of follow-up was 4.86 years. Conclusion FNSs are rare and may be difficult to distinguish from VS preoperatively. Surgical findings that should raise concern include spontaneous action potentials during drilling the bony IAC, absence of a plane of dissection between the facial nerve and tumor, or stimulation of the tumor capsule.

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PGE2 hyperpolarizes gallbladder neurons and inhibits synaptic potentials in gallbladder ganglia

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1998.274.3.g493 ◽

1998 ◽

Vol 274 (3) ◽

pp. G493-G502 ◽

Cited By ~ 6

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.

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2000.279.3.g622 ◽

2000 ◽

Vol 279 (3) ◽

pp. G622-G630 ◽

Cited By ~ 16

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.

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Spontaneous electrical rhythmicity and the role of the sarcoplasmic reticulum in the excitability of guinea pig gallbladder smooth muscle cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00310.2005 ◽

2006 ◽

Vol 290 (4) ◽

pp. G655-G664 ◽

Cited By ~ 23

Author(s):

Onesmo B. Balemba ◽

Matthew J. Salter ◽

Thomas J. Heppner ◽

Adrian D. Bonev ◽

Mark T. Nelson ◽

...

Keyword(s):

Smooth Muscle ◽

Sarcoplasmic Reticulum ◽

Action Potentials ◽

Cyclopiazonic Acid ◽

Cellular Mechanisms ◽

Voltage Dependent ◽

Spontaneous Action ◽

Potential Activity ◽

Spontaneous Action Potentials

Spontaneous action potentials and Ca2+ transients were investigated in intact gallbladder preparations to determine how electrical events propagate and the cellular mechanisms that modulate these events. Rhythmic phasic contractions were preceded by Ca2+ flashes that were either focal (limited to one or a few bundles), multifocal (occurring asynchronously in several bundles), or global (simultaneous flashes throughout the field). Ca2+ flashes and action potentials were abolished by inhibiting sarcoplasmic reticulum (SR) Ca2+ release via inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3] channels with 2-aminoethoxydiphenyl borate and xestospongin C or by inhibiting voltage-dependent Ca2+ channels (VDCCs) with nifedipine or diltiazem or nisoldipine. Inhibiting ryanodine channels with ryanodine caused multiple spikes superimposed upon plateaus of action potentials and extended quiescent periods. Depletion of SR Ca2+ stores with thapsigargin or cyclopiazonic acid increased the frequency and duration of Ca2+ flashes and action potentials. Acetylcholine, carbachol, or cholecystokinin increased synchronized and increased the frequency of Ca2+ flashes and action potentials. The phospholipase C (PLC) inhibitor U-73122 did not affect Ca2+ flash or action potential activity but inhibited the excitatory effects of acetylcholine on these events. These results indicate that Ca2+ flashes correspond to action potentials and that rhythmic excitation in the gallbladder is multifocal among gallbladder smooth muscle bundles and can be synchronized by excitatory agonists. These events do not depend on PLC activation, but agonist stimulation involves activation of PLC. Generation of these events depends on Ca2+ entry via VDCCs and on Ca2+ mobilization from the SR via Ins(1,4,5)P3 channels.

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

Journal of Applied Physiology ◽

10.1152/jappl.1987.62.1.175 ◽

1987 ◽

Vol 62 (1) ◽

pp. 175-179 ◽

Cited By ~ 15

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.

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