scholarly journals Calcium-induced calcium release regulates action potential generation in guinea-pig sympathetic neurones

2004 ◽  
Vol 555 (3) ◽  
pp. 627-635 ◽  
Author(s):  
Sarah A. Locknar ◽  
Karen L. Barstow ◽  
John D. Tompkins ◽  
Laura A. Merriam ◽  
Rodney L. Parsons
2001 ◽  
Vol 281 (6) ◽  
pp. R1792-R1800 ◽  
Author(s):  
Lili Zhang ◽  
John D. Tompkins ◽  
John C. Hancock ◽  
Donald B. Hoover

—Application of substance P (SP) to intracardiac neurons of the guinea pig causes slow depolarization and increases neuronal excitability. The present study was done to determine the influence of SP on fast excitatory responses of intracardiac neurons to ACh. Intracellular recording methods were used to measure responses of intracardiac neurons in whole mount preparations of atrial ganglionated nerve plexus from guinea pig hearts. Local pressure ejection of 100 μM SP (1 s) from a glass micropipette caused slow depolarization of all neurons ( n = 38) and triggered action potential generation in 47% of the cells tested. Bath application of SP (0.5–100 μM) caused a dose-dependent depolarization of intracardiac neurons but rarely evoked action potentials, even at the highest concentration. However, such treatment with SP enhanced nicotinic responses evoked by local pressure ejections of ACh (10 mM, 10- to 100-ms duration) in 77% of intracardiac neurons studied ( n = 52). A significant increase in amplitude of ACh-evoked fast depolarization occurred during treatment with 0.5 μM SP (13.0 ± 1.8 mV for control vs. 17.7 ± 1.9 mV with SP present, n = 7, P = 0.019). At higher concentrations of SP, enhancement of the response to ACh resulted mainly in action potential generation. However, responses to ACh were attenuated by SP in 15% of the intracardiac neurons studied. This attenuation occurred primarily during exposure to 10 and 100 μM SP and was manifest as a reduction in amplitude of nicotinic fast depolarization or inhibition of ACh-evoked action potentials. These findings support the conclusion that SP could function as a neuromodulator and neurotransmitter in intracardiac ganglia of the guinea pig.


2005 ◽  
Vol 289 (3) ◽  
pp. G501-G507 ◽  
Author(s):  
Georgi V. Petkov ◽  
Onesmo B. Balemba ◽  
Mark T. Nelson ◽  
Gary M. Mawe

The action potential in gallbladder smooth muscle (GBSM) is caused by Ca2+ entry through voltage-dependent Ca2+ channels (VDCC), which contributes to the GBSM contractions. Action potential generation in GBSM is critically dependent on the resting membrane potential (about −50 mV), which is ∼35 mV more positive of the K+ equilibrium potential. We hypothesized that a tonic, depolarizing conductance is present in GBSM and contributes to the regulation of the resting membrane potential and action potential frequency. GBSM cells were isolated from guinea pig gallbladders, and the whole cell patch-camp technique was used to record membrane currents. After eliminating the contribution of VDCC and K+ channels, we identified a novel spontaneously active cation conductance ( Icat) in GBSM. This Icat was mediated predominantly by influx of Na+. Na+ substitution with N-methyl-d-glucamine (NMDG), a large relatively impermeant cation, caused a negative shift in the reversal potential of the ramp current and reduced the amplitude of the inward current at −50 mV by 65%. Membrane potential recordings with intracellular microelectrodes or in current-clamp mode of the patch-clamp technique indicated that the inhibition of Icat conductance by NMDG is associated with membrane hyperpolarization and inhibition of action potentials. Extracellular Ca2+, Mg2+, and Gd3+ attenuated the Icat in GBSM. Muscarinic stimulation did not activate the Icat. Our results indicate that, in GBSM, an Na+-permeable channel contributes to the maintenance of the resting membrane potential and action potential generation and therefore plays a critical role in the regulation of GBSM excitability and contractility.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin Grieb ◽  
Sivaranjan Uppala ◽  
Gal Sapir ◽  
David Shaul ◽  
J. Moshe Gomori ◽  
...  

AbstractDirect and real-time monitoring of cerebral metabolism exploiting the drastic increase in sensitivity of hyperpolarized 13C-labeled metabolites holds the potential to report on neural activity via in-cell metabolic indicators. Here, we followed the metabolic consequences of curbing action potential generation and ATP-synthase in rat cerebrum slices, induced by tetrodotoxin and oligomycin, respectively. The results suggest that pyruvate dehydrogenase (PDH) activity in the cerebrum is 4.4-fold higher when neuronal firing is unperturbed. The PDH activity was 7.4-fold reduced in the presence of oligomycin, and served as a pharmacological control for testing the ability to determine changes to PDH activity in viable cerebrum slices. These findings may open a path towards utilization of PDH activity, observed by magnetic resonance of hyperpolarized 13C-labeled pyruvate, as a reporter of neural activity.


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