Peak Current Density (peak + current_density)

Distribution by Scientific Domains


Selected Abstracts


Characterization of the A-type potassium current in murine gastric antrum

THE JOURNAL OF PHYSIOLOGY, Issue 2 2002
Gregory C. Amberg
A-type currents are rapidly inactivating potassium currents that operate at subthreshold potentials. A-type currents have not been reported to occur in the phasic muscles of the stomach. We used conventional voltage-clamp techniques to identify and characterize A-type currents in myocytes isolated from the murine antrum. A-type currents were robust in these cells, with peak current densities averaging 30 pA pF,1 at 0 mV. These currents underwent rapid inactivation with a time constant of 83 ms at 0 mV. Recovery from inactivation at ,80 mV was rapid, with a time constant of 252 ms. The A-type current was blocked by 4-aminopyridine (4-AP) and was inhibited by flecainide, with an IC50 of 35 ,M. The voltage for half-activation was ,26 mV, while the voltage of half-inactivation was ,65 mV. There was significant activation and incomplete inactivation at potentials positive to ,60 mV, which is suggestive of sustained current availability in this voltage range. Under current-clamp conditions, exposure to 4-AP or flecainide depolarized the membrane potential by 7-10 mV. In intact antral tissue preparations, flecainide depolarized the membrane potential between slow waves by 5 mV; changes in slow waves were not evident. The effect of flecainide was not abolished by inhibiting enteric neurotransmission or by blocking delayed rectifier and ATP-sensitive K+ currents. Transcripts encoding Kv4 channels were detected in isolated antral myocytes by RT-PCR. Immunocytochemistry revealed intense Kv4.2- and Kv4.3-like immunoreactivity in antral myocytes. These data suggest that the A-type current in murine antral smooth muscle cells is likely to be due to Kv4 channels. This current contributes to the maintenance of negative resting membrane potentials. [source]


Protein kinase A modulates A-type potassium currents of larval zebrafish (Danio rerio) white muscle fibres

ACTA PHYSIOLOGICA, Issue 2 2009
C. A. Coutts
Abstract Aims:, Potassium (K+) channels are involved in regulating cell excitability and action potential shape. To our knowledge, very little is known about the modulation of A-type K+ currents in skeletal muscle fibres. Therefore, we sought to determine whether K+ currents of zebrafish white skeletal muscle were modulated by protein kinase A (PKA). Methods:, Pharmacology and whole-cell patch clamp were used to examine A-type K+ currents and action potentials associated with zebrafish white skeletal muscle fibres. Results:, Activation of PKA by a combination of forskolin + 3-isobutyl-1-methylxanthine (Fsk + IBMX) decreased the peak current density by ,60% and altered the inactivation kinetics of A-type K+ currents. The specific PKA inhibitor H-89 partially blocked the Fsk + IBMX-induced reduction in peak current density, but had no effect on the change in decay kinetics. Fsk + IBMX treatment did not shift the activation curve, but it significantly reduced the slope factor of activation. Activation of PKA by Fsk + IBMX resulted in a negative shift in the V50 of inactivation. H-89 prevented all Fsk + IBMX-induced changes in the steady-state properties of K+ currents. Application of Fsk + IBMX increased action potential amplitude, but had no significant effect on action potential threshold, half width or recovery rate, when fibres were depolarized with single pulses, paired pulses or with high-frequency stimuli. Conclusion:, PKA modulates the A-type K+ current in zebrafish skeletal muscle and affects action potential properties. Our results provide new insights into the role of A-type K+ channels in muscle physiology. [source]


Development of ionic currents of zebrafish slow and fast skeletal muscle fibers

DEVELOPMENTAL NEUROBIOLOGY, Issue 3 2006
Christopher A. Coutts
Abstract Voltage-gated Na+ and K+ channels play key roles in the excitability of skeletal muscle fibers. In this study we investigated the steady-state and kinetic properties of voltage-gated Na+ and K+ currents of slow and fast skeletal muscle fibers in zebrafish ranging in age from 1 day postfertilization (dpf) to 4,6 dpf. The inner white (fast) fibers possess an A-type inactivating K+ current that increases in peak current density and accelerates its rise and decay times during development. As the muscle matured, the V50s of activation and inactivation of the A-type current became more depolarized, and then hyperpolarized again in older animals. The activation kinetics of the delayed outward K+ current in red (slow) fibers accelerated within the first week of development. The tail currents of the outward K+ currents were too small to allow an accurate determination of the V50s of activation. Red fibers did not show any evidence of inward Na+ currents; however, white fibers expressed Na+ currents that increased their peak current density, accelerated their inactivation kinetics, and hyperpolarized their V50 of inactivation during development. The action potentials of white fibers exhibited significant changes in the threshold voltage and the half width. These findings indicate that there are significant differences in the ionic current profiles between the red and white fibers and that a number of changes occur in the steady-state and kinetic properties of Na+ and K+ currents of developing zebrafish skeletal muscle fibers, with the most dramatic changes occurring around the end of the first day following egg fertilization. © 2005 Wiley Periodicals, Inc. J Neurobiol, 2006 [source]


The action of Lambert,Eaton myasthenic syndrome immunoglobulin G on cloned human voltage-gated calcium channels

MUSCLE AND NERVE, Issue 5 2002
Ashwin Pinto MRCP, DPhil
Abstract In the Lambert,Eaton myasthenic syndrome (LEMS), immunoglobulin G (IgG) autoantibodies to presynaptic voltage-gated calcium channels (VGCCs) at the neuromuscular junction lead to a reduction in nerve-evoked release of neurotransmitter and muscle weakness. We have examined the action of LEMS IgGs on cloned human VGCCs stably expressed in transfected human embryonic kidney (HEK293) cell lines: 10,13 (,1A-2, ,2b,, ,4a) and C2D7 (,1B-1 , ,2b,, ,1b). All LEMS IgGs studied showed surface binding to [125I]-,-CTx-MVIIC-labeled VGCCs in the ,1A cell line and two of six IgGs showed surface binding to [125I]-,-CTx-GVIA-labeled VGCCs in the ,1B cell line. We next studied the effect of LEMS IgGs (2 mg/ml) on whole-cell calcium currents in the ,1A and ,1B cell lines. Overnight treatment of ,1A (10,13) cells with LEMS IgGs led to a significant reduction in peak current density without alteration of the current,voltage relationship or the voltage dependence of steady-state inactivation. In contrast, LEMS IgGs did not reduce peak current density in the ,1B cell line. Overall these data demonstrate the specificity of LEMS IgGs for the ,1A cell line and suggest that LEMS IgGs bind to and downregulate VGCCs in this cell line. Although several LEMS IgGs can be shown to bind to the ,1B (C2D7) cell line, no functional effects were seen on this channel. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25: 000,000, 2002 [source]