scholarly journals Membrane Time Constant During Internal Defibrillation Strength Shocks in Intact Heart: Effects of Na+and Ca2+Channel Blockers

2009 ◽  
Vol 20 (1) ◽  
pp. 85-92 ◽  
Author(s):  
KENT A. MOWREY ◽  
IGOR R. EFIMOV ◽  
YUANNA CHENG
1998 ◽  
Vol 275 (2) ◽  
pp. H551-H561 ◽  
Author(s):  
Hugh W. L. Bethell ◽  
Jamie I. Vandenberg ◽  
Gerry A. Smith ◽  
Andrew A. Grace

Myocardial ischemia, primarily a metabolic insult, is also defined by altered cardiac mechanical and electrical activity. We have investigated the metabolic contributions to the electrophysiological changes during low-flow ischemia (7.5% of the control flow) using31P NMR spectroscopy to monitor metabolic parameters, suction electrodes to study epicardial monophasic action potentials, and 86Rb as a tracer for K+-equivalent efflux during low-flow ischemia in the Langendorff-perfused ferret heart. Shortening of the action potential duration at 90% repolarization (APD90) was most marked between 1 and 5 min after induction of ischemia, at which time it shortened from 261 ± 4 to 213 ± 8 ms. The period of marked APD90 shortening was accompanied by a fivefold increase in the rate of86Rb efflux, both of which were inhibited by the ATP-sensitive K+(KATP)-channel blockers glibenclamide and 5-hydroxydecanoate (5-HD), as well as by a significant fall in intracellular pH (pHi) from 7.14 ± 0.02 to 6.83 ± 0.03 but no change in intracellular ATP concentration ([ATP]i). We therefore investigated whether a fall in pHi could be the metabolic change responsible for modulating cardiac KATP channel activity in the intact heart during ischemia. Both metabolic (30 mM lactate added to extracellular solution) and respiratory ([Formula: see text] increased to 15%) acidosis caused an initial lengthening of APD90 to 112 ± 1.5 and 113 ± 0.9%, respectively, followed by shortening during continued acidosis to 106 ± 1.2 and 106 ± 1.4%, respectively. The shortening of APD90 during continued acidosis was inhibited by glibenclamide, consistent with acidosis causing activation of KATP channels at normal [ATP]i. The similar responses to metabolic (induced by adding either l- or d-lactate) and respiratory acidosis suggest that lactate has no independent metabolic effect on action potential repolarization.


1985 ◽  
Vol 54 (4) ◽  
pp. 807-817 ◽  
Author(s):  
D. Durand ◽  
P. Carlen

The electronic parameters of nerve cells in the dentate gyrus following long-term ingestion of ethanol were studied in vitro. The ethanol was administered in a liquid diet for a period of 20 wk followed by a 3-wk withdrawal period. A control group received a similar diet with the ethanol replaced by maltose-dextrins. Intracellular recordings were obtained from 44 neurons, and the voltage decays following current injections were analyzed with a recent electrical model of granule cells to take into account a somatic shunt already detected in previous studies. The new model accurately accounted for the fast voltage transients and showed that the membrane time constant in the dendrites is, on average, five times larger than the somatic time constant. Injection of horseradish peroxidase into the neurons for the morphological analysis showed that neurons in the ethanol group have a longer dendritic tree than neurons in the control group. Estimation of the membrane surface area showed that the membrane area in the dendrites is at least 60% greater (in both control and ethanol groups) when the membrane foldings and irregularities are taken into account. The results of the modeling analysis showed that the membrane time constant and the input resistance are not affected by ethanol. However, the membrane resistance is significantly increased in the ethanol group (6,632 versus 18,460 omega X cm2), and the capacitance is significantly decreased (4.48 versus 1.71 microF/cm2). The electrotonic length is also increased by chronic ethanol treatment (0.85 versus 0.94). Higher values of membrane specific resistance (Rm) mean larger transmission coefficients. However, since the neurons from the ethanol group are on average longer than neurons in the control group, it is suggested that the change in Rm compensates for the increase in the length of the dendrites, thereby maintaining a value of the electrotonic length under 1.0. The observed changes in the passive parameters are in opposite direction from the recently measured effect of acute doses of ethanol on hippocampal neurons. These results support a model of chronic alcohol intake where homeostatic adaptive changes lead to the development of long-term changes in cellular physiology.


1995 ◽  
Vol 74 (3) ◽  
pp. 1200-1211 ◽  
Author(s):  
P. H. Torkkeli ◽  
A. S. French

1. Although rapid adaptation is a widespread feature of sensory receptors, its ionic basis has not been clearly established in any touch receptor, because their small sizes have severely restricted the range of experiments tat can be performed. In the cockroach tactile spine, intracellular voltage-clamp recordings are now possible. 2. The basic electrophysiological properties of the cockroach femoral tactile spine neuron were studied using discontinuous (switching) single-electrode current- and voltage-clamp recordings. A slowly inactivating voltage-sensitive K+ outward current was detected after the major inward currents were blocked with tetrodotoxin. 3. The total outward current activated in < 1 ms at voltages above 0 mV. At moderate depolarizations it did not inactivate, but at higher depolarizations an inactivation time constant of approximately 260 ms was measured. Some recordings also revealed an additional, slower inactivation time constant of approximately 2.5 s. 4. More than half of the voltage-sensitive K+ outward current could be blocked with the Ca2+ channel blockers Co2+ and Cd2+. Tetraethylammonium chloride (TEA) also reduced the amplitude of the outward current to about half of its original amplitude. The actions of both blockers were reversible and probably reflect overlapping blockades of two separate outward currents. 5. The reversal potentials of the currents that remained after block with Co2+ (-91.7 mV) or TEA (-86.8 mV) were both near the K+ equilibrium potential expected for the tactile spine neuron. The voltage dependencies of activation of the Co(2+)- and TEA-resistant currents were both well fitted by Boltzmann distributions, giving values of half maximal activation (V50) equal to -34.5 mV for the Co(2+)-resistant current and -51.3 mV for the TEA-resistant current. 6. Current-clamp recordings revealed that the TEA-sensitive K+ current was the major component of action potential repolarization but that it did not effect the frequency of action potentials evoked by steady depolarization. On the other hand, blockers of Ca(2+)-sensitive K+ currents (Cd2+, Co2+, or charybdotoxin) reduced adaptation and increased the frequency of action potentials significantly but did not effect the duration or amplitude of individual action potentials.


1989 ◽  
Vol 62 (5) ◽  
pp. 1102-1112 ◽  
Author(s):  
J. D. Dickman ◽  
M. J. Correia

1. The horizontal semicircular canals of anesthetized (barbiturate/ketamine) pigeons were mechanically stimulated by the use of a piezoelectric micropusher that provided controlled indentation of the surgically exposed membranous horizontal semicircular duct. 2. Extracellular action potentials from single horizontal semicircular canal afferent (HCA) fibers were recorded during sinusoidal mechanical stimulation. This method of stimulation was shown in the companion paper to produce equivalent responses to those produced by rotation for frequencies ranging from 0.01 to 10 Hz. 3. Sinusoidal mechanical stimulation produced clearly entrained action potentials in some HCA fibers up to a frequency of 400 Hz (highest stimulus frequency tested), with stimulus probe displacements of +/- 1.0 and +/- 2.5 microns. Thirty-four HCA fibers were thoroughly studied. 4. For most HCA fibers, the number of action potentials per stimulus cycle decreased as stimulus frequency increased, until only one action potential per stimulus cycle was elicited. The point at which only one spike per stimulus cycle was observed was dependent on both the fiber's resting mean discharge rate (MDR) and the fiber's coefficient of variation (CV) obtained during the MDR. 5. Dynamic response properties of individual HCA fibers were found to be correlated with the fiber's CV and the resting level MDR. Neurons with lower CV values had less adaptation, higher short time constants, and lower high corner frequencies than did neurons with high CV values. For a given CV class of HCA fibers, neurons with higher MDRs had more enhanced gains and more advanced phase shifts at high stimulus frequencies than did neurons with lower MDRs. 6. Transfer function parameters affecting the dynamics of the high-frequency response were derived from the mean gain and phase shift values of regular-, intermediate-, and irregular-firing HCA fibers. Best-fit short time constant (tau S) values of 4.6, 1.9, and 2.0 ms; hair cell membrane time constant (tau M) values of 10.3, 13, and 7 ms; excitatory postsynaptic membrane time constant (tau E) values of 0.8, 0.4, and 0.5 ms; and synaptic delay time constant (tau D) values of 0.5, 0.5, and 1.4 ms were determined for regular, intermediate, and irregular classes of HCA fibers, respectively. 7. The values of 4.6, 1.9, and 2.0 ms derived for the regular, intermediate, and irregular afferents would suggest upper-corner frequencies of 35, 84, and 80 Hz for these classes of HCA fibers, respectively.


2013 ◽  
Vol 110 (2) ◽  
pp. 307-321 ◽  
Author(s):  
John H. Wittig ◽  
Kwabena Boahen

A fundamental question in neuroscience is how neurons perform precise operations despite inherent variability. This question also applies to neuromorphic engineering, where low-power microchips emulate the brain using large populations of diverse silicon neurons. Biological neurons in the auditory pathway display precise spike timing, critical for sound localization and interpretation of complex waveforms such as speech, even though they are a heterogeneous population. Silicon neurons are also heterogeneous, due to a key design constraint in neuromorphic engineering: smaller transistors offer lower power consumption and more neurons per unit area of silicon, but also more variability between transistors and thus between silicon neurons. Utilizing this variability in a neuromorphic model of the auditory brain stem with 1,080 silicon neurons, we found that a low-voltage-activated potassium conductance ( gKL) enables precise spike timing via two mechanisms: statically reducing the resting membrane time constant and dynamically suppressing late synaptic inputs. The relative contribution of these two mechanisms is unknown because blocking gKL in vitro eliminates dynamic adaptation but also lengthens the membrane time constant. We replaced gKL with a static leak in silico to recover the short membrane time constant and found that silicon neurons could mimic the spike-time precision of their biological counterparts, but only over a narrow range of stimulus intensities and biophysical parameters. The dynamics of gKL were required for precise spike timing robust to stimulus variation across a heterogeneous population of silicon neurons, thus explaining how neural and neuromorphic systems may perform precise operations despite inherent variability.


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