Heterogeneity of 4-aminopyridine-sensitive current in rabbit sinoatrial node cells

1999 ◽  
Vol 276 (4) ◽  
pp. H1295-H1304 ◽  
Author(s):  
Haruo Honjo ◽  
Ming Lei ◽  
Mark R. Boyett ◽  
Itsuo Kodama
Keyword(s):  
Membrane Potential ◽  
Regional Differences ◽  
Sinoatrial Node ◽  
Pacemaker Cells ◽  
Electrophysiological Properties ◽  
Sa Node ◽  
Slope Factor ◽  
Ionic Mechanisms ◽  
Rabbit Sinoatrial Node ◽  
Cell Capacitance

The electrophysiological properties of sinoatrial (SA) node pacemaker cells vary in different regions of the node. In this study, we have investigated variation of the 4-aminopyridine (4-AP)-sensitive current as a function of the size (as measured by the cell capacitance) of SA node cells to elucidate the ionic mechanisms. The 10 mM 4-AP-sensitive current recorded from rabbit SA node cells was composed of transient and sustained components ( I trans and I sus, respectively). The activation and inactivation properties [activation: membrane potential at which conductance is half-maximally activated ( V h) = 19.3 mV, slope factor ( k) = 15.0 mV; inactivation: V h= −31.5 mV, k = 7.2 mV] as well as the density of I trans (9.0 pA/pF on average at +50 mV) were independent of cell capacitance. In contrast, the density of I sus (0.97 pA/pF on average at +50 mV) was greater in larger cells, giving rise to a significant correlation with cell capacitance. The greater density of I sus in larger cells (presumably from the periphery) can explain the shorter action potential in the periphery of the SA node compared with that in the center. Thus variation of the 4-AP-sensitive current may be involved in regional differences in repolarization within the SA node.

Ionic basis for endogenous rhythmic patterns induced by activation of N-methyl-D-aspartate receptors in neurons of the rat nucleus tractus solitarii

1993 ◽  
Vol 70 (6) ◽  
pp. 2379-2390 ◽  
Author(s):  
F. Tell ◽  
A. Jean
Keyword(s):  
Membrane Potential ◽  
Neuronal Firing ◽  
Calcium Currents ◽  
Nucleus Tractus Solitarii ◽  
Repetitive Firing ◽  
Potential Range ◽  
Electrophysiological Properties ◽  
Ionic Mechanisms ◽  
Discharge Patterns

1. Activation of N-methyl-D-aspartate (NMDA) receptors in caudal nucleus tractus solitarii (cNTS) neurons elicited endogenous rhythmic activities. We used an in vitro brain stem slice preparation to determine the ionic mechanisms underlying the generation of these activities. 2. Using intracellular recordings, we found several ionic conductances to be responsible for the electrophysiological properties of cNTS neurons. After addition of tetrodotoxin (TTX) to the perfusate, cNTS neurons were still able to generate action potentials (APs). Because these APs were suppressed by the addition of cobalt or by the reduction of calcium, they were likely due to calcium currents (ICa). In addition, the amplitude of the afterhyperpolarization (AHP) that followed a train of TTX-resistant APs was reduced in both low-calcium and cobalt-containing saline. It was therefore suggested that calcium-activated potassium (IKCa) currents were involved in the AHP. Accordingly, application of apamin, a blocker of slow IKCa, also decreased the AHP. cNTS neurons exhibited a delayed excitation phenomenon, characterized by a ramplike depolarization that delayed the onset of neuronal firing, when they were depolarized from hyperpolarizing potential. The underlying current was presumed to be an A-current (IKA), because this phenomenon was suppressed during application of 4-aminopyridine (4-AP). 3. Application of NMDA elicited different types of discharge patterns in cNTS neurons: a repetitive firing at depolarized levels of membrane potential (above -60 mV) and rhythmic patterns characterized by either rhythmic bursting or rhythmic single discharges at hyperpolarized levels (within membrane potential range of -60 to -85 mV). In all neurons, rhythmic patterns were superimposed on oscillations of membrane potential. They were characterized by a sudden shift of membrane potential, followed by a ramp-shaped phase of depolarization that preceded spike elicitation. Addition of TTX to the saline did not suppress NMDA-induced oscillations. Therefore rhythmic patterns were not driven by synaptic mechanisms but resulted from endogenous properties of cNTS neurons. 4. APs superimposed on NMDA-induced depolarizations presented the same characteristics as those elicited by positive current pulses. NMDA-elicited oscillations of membrane potential were eliminated by removing magnesium from the saline. Therefore oscillation generation was based primarily on the NMDA channel properties. 5. Intrinsic conductances of cNTS neurons interacted with NMDA-gated conductances to shape the depolarization waveform. Because removal of calcium from the saline suppressed endogenous oscillations, ICa currents were required for the expression of rhythmic activities. IKCa currents were involved in the repolarization phase of oscillations because apamin increased the duration of the oscillations.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Properties and physiological function of Ca2+-dependent K+ currents in uniglomerular olfactory projection neurons

2016 ◽  
Vol 115 (5) ◽  
pp. 2330-2340 ◽  
Author(s):  
Cathleen Bradler ◽  
Ben Warren ◽  
Viktor Bardos ◽  
Sabine Schleicher ◽  
Andreas Klein ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Intracellular Signaling ◽  
Periplaneta Americana ◽  
Bk Channels ◽  
Adult Brain ◽  
Insect Brain ◽  
Projection Neurons ◽  
Membrane Excitability ◽  
Electrophysiological Properties ◽  
Ionic Mechanisms

Ca2+-activated potassium currents [ IK(Ca)] are an important link between the intracellular signaling system and the membrane potential, which shapes intrinsic electrophysiological properties. To better understand the ionic mechanisms that mediate intrinsic firing properties of olfactory uniglomerular projection neurons (uPNs), we used whole cell patch-clamp recordings in an intact adult brain preparation of the male cockroach Periplaneta americana to analyze IK(Ca). In the insect brain, uPNs form the principal pathway from the antennal lobe to the protocerebrum, where centers for multimodal sensory processing and learning are located. In uPNs the activation of IK(Ca) was clearly voltage and Ca2+ dependent. Thus under physiological conditions IK(Ca) is strongly dependent on Ca2+ influx kinetics and on the membrane potential. The biophysical characterization suggests that IK(Ca) is generated by big-conductance (BK) channels. A small-conductance (SK) channel-generated current could not be detected. IK(Ca) was sensitive to charybdotoxin (CTX) and iberiotoxin (IbTX) but not to apamin. The functional role of IK(Ca) was analyzed in occlusion experiments under current clamp, in which portions of IK(Ca) were blocked by CTX or IbTX. Blockade of IK(Ca) showed that IK(Ca) contributes significantly to intrinsic electrophysiological properties such as the action potential waveform and membrane excitability.

Regional differences in effects of 4-aminopyridine within the sinoatrial node

1998 ◽  
Vol 275 (4) ◽  
pp. H1158-H1168 ◽  
Author(s):  
M. R. Boyett ◽  
H. Honjo ◽  
M. Yamamoto ◽  
M. R. Nikmaram ◽  
R. Niwa ◽  
...  
Keyword(s):  
Action Potential ◽  
Regional Differences ◽  
Sinoatrial Node ◽  
Outward Current ◽  
Peripheral Tissue ◽  
Transient Outward Current ◽  
Pacemaker Activity ◽  
Small Ball ◽  
Tissue Differences ◽  
Rabbit Sinoatrial Node

4-Aminopyridine (4-AP)-sensitive transient outward current ( I to) has been observed in the sinoatrial node, but its role is unknown. The effect of block of I to by 5 mM 4-AP on small ball-like tissue preparations (diameter ∼0.3–0.4 mm) from different regions of the rabbit sinoatrial node has been investigated. 4-AP elevated the plateau, prolonged the action potential, and decreased the maximum diastolic potential. Effects were greater in tissue from the periphery of the node than from the center. In peripheral tissue, 4-AP abolished the action potential notch, if present. 4-AP slowed pacemaker activity of peripheral tissue but accelerated that of central tissue. Differences in the response to 4-AP were also observed between tissue from more superior and inferior regions of the node. In the intact sinoatrial node, 4-AP resulted in a shift of the leading pacemaker site consistent with the regional differences in the response to 4-AP. It is concluded that 4-AP-sensitive outward current plays a major role in action potential repolarization and pacemaker activity in the sinoatrial node and that its role varies regionally.

Removal of sialic acid alters both T- and L-type calcium currents in cardiac myocytes

1991 ◽  
Vol 260 (3) ◽  
pp. H735-H743 ◽  
Author(s):  
B. Fermini ◽  
R. D. Nathan
Keyword(s):  
Sialic Acid ◽  
Sinoatrial Node ◽  
Calcium Currents ◽  
Pacemaker Cells ◽  
Patch Clamp Technique ◽  
Inactivation Curve ◽  
Node Removal ◽  
Rabbit Sinoatrial Node ◽  
Ca2 Channels ◽  
In Cells

The whole cell configuration of the patch-clamp technique was used to test the hypothesis that the presence of sialic acid residues influences both T- and L-type Ca2+ currents (ICa,T and ICa,L) in cultured pacemaker cells isolated from the rabbit sinoatrial node. Removal of these anionic sugar moieties by neuraminidase (1.0 U/ml for 5-20 min) increased ICa,T in five of nine cells (by a factor of 2.2-5.1) and ICa,L in three of six cells (by a factor of 1.2-1.6). In cells that did not exhibit such an increase, the enzyme reduced ICa,T but had no significant effect on ICa,L. In cells that exhibited an increase in ICa,T, exposure to neuraminidase also shifted the activation curve to more negative potentials and increased the slope of the inactivation curve. The enzyme did not influence the gating of ICa,L or the rates of inactivation of either ICa,T or ICa,L. The enhancement of ICa,T and ICa,L could not be mimicked by including neuraminidase in the patch pipette or by adding a contaminant of the enzyme preparation, phospholipase C, to the bath. When external Ca2+ was replaced by Ba2+, neither ICa,T nor ICa,L was increased significantly by neuraminidase. It is proposed that by removing sialic acid residues neuraminidase might directly alter the gating of T-type Ca2+ channels. On the other hand, the increased amplitudes of ICa,T and ICa,L might be due to a rise in intracellular Ca2+.

Regional differences in effects of E-4031 within the sinoatrial node

1999 ◽  
Vol 276 (3) ◽  
pp. H793-H802 ◽  
Author(s):  
I. Kodama ◽  
M. R. Boyett ◽  
M. R. Nikmaram ◽  
M. Yamamoto ◽  
H. Honjo ◽  
...  
Keyword(s):  
Action Potential ◽  
Electrical Activity ◽  
Spontaneous Activity ◽  
Regional Differences ◽  
Sinoatrial Node ◽  
Peripheral Tissue ◽  
Delayed Rectifier ◽  
Small Ball ◽  
Rabbit Sinoatrial Node ◽  
Diastolic Potential

Effects of block of the rapid delayed rectifier K+current ( I K,r) by E-4031 on the electrical activity of small ball-like tissue preparations from different regions of the rabbit sinoatrial node were measured. The effects of partial block of I K,r by 0.1 μM E-4031 varied in different regions of the node. In tissue from the center of the node spontaneous activity was generally abolished, whereas in tissue from the periphery spontaneous activity persisted, although the action potential was prolonged, the maximum diastolic potential was decreased, and the spontaneous activity slowed. After partial block of I K,r, the electrical activity of peripheral tissue was more like that of central tissue under normal conditions. One possible explanation of these findings is that the density of I K,r is greater in the periphery of the node; this would explain the greater resistance of peripheral tissue to I K,r block and help explain why, under normal conditions, the maximum diastolic potential is more negative, the action potential is shorter, and pacemaking is faster in the periphery.

A mathematical model of a rabbit sinoatrial node cell

1994 ◽  
Vol 266 (3) ◽  
pp. C832-C852 ◽  
Author(s):  
S. S. Demir ◽  
J. W. Clark ◽  
C. R. Murphey ◽  
W. R. Giles
Keyword(s):  
Mathematical Model ◽  
Sinoatrial Node ◽  
Surface Membrane ◽  
Recent Experimental Data ◽  
Pacemaker Cells ◽  
Diffusion Limited ◽  
Electrophysiological Responses ◽  
Sinoatrial Node Cell ◽  
Rabbit Sinoatrial Node

A mathematical model for the electrophysiological responses of a rabbit sinoatrial node cell that is based on whole cell recordings from enzymatically isolated single pacemaker cells at 37 degrees C has been developed. The ion channels, Na(+)-K+ and Ca2+ pumps, and Na(+)-Ca2+ exchanger in the surface membrane (sarcolemma) are described using equations for these known currents in mammalian pacemaker cells. The extracellular environment is treated as a diffusion-limited space, and the myoplasm contains Ca(2+)-binding proteins (calmodulin and troponin). Original features of this model include 1) new equations for the hyperpolarization-activated inward current, 2) assessment of the role of the transient-type Ca2+ current during pacemaker depolarization, 3) inclusion of an Na+ current based on recent experimental data, and 4) demonstration of the possible influence of pump and exchanger currents and background currents on the pacemaker rate. This model provides acceptable fits to voltage-clamp and action potential data and can be used to seek biophysically based explanations of the electrophysiological activity in the rabbit sinoatrial node cell.

Cesium Effects on if and iK in Rabbit Sinoatrial Node Myocytes: Implications for SA Node Automaticity

1998 ◽  
Vol 32 (5) ◽  
pp. 783-790 ◽  
Author(s):  
Y. M. Liu ◽  
H. Yu ◽  
C-Z. Li ◽  
I. S. Cohen ◽  
M. Vassalle
Keyword(s):  
Sinoatrial Node ◽  
Sa Node ◽  
Rabbit Sinoatrial Node
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