scholarly journals Density of voltage-gated potassium channels is a bifurcation parameter in pyramidal neurons

2015 ◽  
Vol 113 (2) ◽  
pp. 537-549 ◽  
Author(s):  
Hugo Zeberg ◽  
Hugh P. C. Robinson ◽  
Peter Århem
Keyword(s):  
Outward Current ◽  
Pyramidal Cells ◽  
Theoretical Work ◽  
K Channel ◽  
Threshold Dynamics ◽  
Bifurcation Parameter ◽  
Channel Density ◽  
Subthreshold Oscillations

Several types of intrinsic dynamics have been identified in brain neurons. Type 1 excitability is characterized by a continuous frequency-stimulus relationship and, thus, an arbitrarily low frequency at threshold current. Conversely, Type 2 excitability is characterized by a discontinuous frequency-stimulus relationship and a nonzero threshold frequency. In previous theoretical work we showed that the density of Kv channels is a bifurcation parameter, such that increasing the Kv channel density in a neuron model transforms Type 1 excitability into Type 2 excitability. Here we test this finding experimentally, using the dynamic clamp technique on Type 1 pyramidal cells in rat cortex. We found that increasing the density of slow Kv channels leads to a shift from Type 1 to Type 2 threshold dynamics, i.e., a distinct onset frequency, subthreshold oscillations, and reduced latency to first spike. In addition, the action potential was resculptured, with a narrower spike width and more pronounced afterhyperpolarization. All changes could be captured with a two-dimensional model. It may seem paradoxical that an increase in slow K channel density can lead to a higher threshold firing frequency; however, this can be explained in terms of bifurcation theory. In contrast to previous work, we argue that an increased outward current leads to a change in dynamics in these neurons without a rectification of the current-voltage curve. These results demonstrate that the behavior of neurons is determined by the global interactions of their dynamical elements and not necessarily simply by individual types of ion channels.

scholarly journals Angiotensin II type 2 receptor regulates ROMK-like K+ channel activity in the renal cortical collecting duct during high dietary K+ adaptation

2014 ◽  
Vol 307 (7) ◽  
pp. F833-F843 ◽  
Author(s):  
Yuan Wei ◽  
Yi Liao ◽  
Beth Zavilowitz ◽  
Jin Ren ◽  
Wen Liu ◽  
...  
Keyword(s):  
Collecting Duct ◽  
No Synthase ◽  
K Channel ◽  
Ang Ii ◽  
Cortical Collecting Duct ◽  
Channel Activity ◽  
High K ◽  
Pka Pathway

The kidney adjusts K+ excretion to match intake in part by regulation of the activity of apical K+ secretory channels, including renal outer medullary K+ (ROMK)-like K+ channels, in the cortical collecting duct (CCD). ANG II inhibits ROMK channels via the ANG II type 1 receptor (AT1R) during dietary K+ restriction. Because AT1Rs and ANG II type 2 receptors (AT2Rs) generally function in an antagonistic manner, we sought to characterize the regulation of ROMK channels by the AT2R. Patch-clamp experiments revealed that ANG II increased ROMK channel activity in CCDs isolated from high-K+ (HK)-fed but not normal K+ (NK)-fed rats. This response was blocked by PD-123319, an AT2R antagonist, but not by losartan, an AT1R antagonist, and was mimicked by the AT2R agonist CGP-42112. Nitric oxide (NO) synthase is present in CCD cells that express ROMK channels. Blockade of NO synthase with N-nitro-l-arginine methyl ester and free NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt completely abolished ANG II-stimulated ROMK channel activity. NO enhances the synthesis of cGMP, which inhibits phosphodiesterases (PDEs) that normally degrade cAMP; cAMP increases ROMK channel activity. Pretreatment of CCDs with IBMX, a broad-spectrum PDE inhibitor, or cilostamide, a PDE3 inhibitor, abolished the stimulatory effect of ANG II on ROMK channels. Furthermore, PKA inhibitor peptide, but not an activator of the exchange protein directly activated by cAMP (Epac), also prevented the stimulatory effect of ANG II. We conclude that ANG II acts at the AT2R to stimulate ROMK channel activity in CCDs from HK-fed rats, a response opposite to that mediated by the AT1R in dietary K+-restricted animals, via a NO/cGMP pathway linked to a cAMP-PKA pathway.

Threshold Firing Frequency–Current Relationships of Neurons in Rat Somatosensory Cortex: Type 1 and Type 2 Dynamics

2004 ◽  
Vol 92 (4) ◽  
pp. 2283-2294 ◽  
Author(s):  
T. Tateno ◽  
A. Harsch ◽  
H. P. C. Robinson
Keyword(s):  
Somatosensory Cortex ◽  
Low Frequency ◽  
Firing Frequency ◽  
Spike Generation ◽  
Low Frequencies ◽  
Subthreshold Oscillations ◽  
Wide Range ◽  
Rat Somatosensory Cortex

Neurons and dynamical models of spike generation display two different types of threshold behavior, with steady current stimulation: type 1 [the firing frequency vs. current ( f– I) relationship is continuous at threshold) and type 2 (discontinuous f– I)]. The dynamics at threshold can have profound effects on the encoding of input as spikes, the sensitivity of spike generation to input noise, and the coherence of population firing. We have examined the f– I and frequency–conductance ( f– g) relationships of cells in layer 2/3 of slices of young (15–21 DIV) rat somatosensory cortex, focusing in detail on the nature of the threshold. Using white-noise stimulation, we also measured firing frequency and interspike interval variability as a function of noise amplitude. Regular-spiking (RS) pyramidal neurons show a type 1 threshold, consistent with their well-known ability to fire regularly at very low frequencies. In fast-spiking (FS) inhibitory interneurons, although regular firing is supported over a wide range of frequencies, there is a clear discontinuity in their f– I relationship at threshold (type 2), which has not previously been highlighted. FS neurons are unable to support maintained periodic firing below a critical frequency fc, in the range of 10 to 30 Hz. Very close to threshold, FS cells switch irregularly between bursts of periodic firing and subthreshold oscillations. These characteristics mean that the dynamics of RS neurons are well suited to encoding inputs into low-frequency firing rates, whereas the dynamics of FS neurons are suited to maintaining and quickly synchronizing to gamma and higher-frequency input.

Synchronous and Asynchronous Exocytosis Induced by Subthreshold High K+ at Cs+-Loaded Terminals of Rat Hippocampal Neurons

2002 ◽  
Vol 87 (3) ◽  
pp. 1222-1233 ◽  
Author(s):  
Fang-Min Lu ◽  
Kenji Kuba
Keyword(s):  
Transmitter Release ◽  
Hippocampal Neurons ◽  
Outward Current ◽  
Current Frequency ◽  
High K ◽  
Type 3 ◽  
A Current ◽  
External K

Transmitter release at Cs+-loaded autaptic terminals was selectively activated by the subthreshold concentration of external K+, and Ca2+ channel types and transmitter pools involved in synchronous and asynchronous exocytosis were studied. When a neuron was depolarized to +30 mV by applying a current through a pipette containing Cs+ for >30 s, a rapid external K+ jump to 3.75–10 mM, otherwise ineffective, produced an outward current (K10 response). K10 responses were initially graded (type-1) and then became a spike and plateau-shape with (type-2) or without a latency (type-3). On repolarization to –60 mV, a high K+ jump induced inward currents (called also K10 response) similar to those at +30 mV, whose shape changed from that of type-3, then type-2 and finally type-1 over 30 min. During a period favorable for inducing a type-3 response, a current similar to this response was generated by a voltage pulse (+ 80 or 90 mV, 20 or 30 ms) to the cell soma. Currents similar to K10 responses were rarely induced by a high K+ jump without a conditioning depolarization except for some cells, but consistently produced when 3 mM Cs+ and 50 μM 4-aminopyridine were externally applied for tens of minutes. Picrotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione with 3-[(RS)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid or Cd2+ in, or Ca2+ removal from, a high-K+ solution blocked all the K10 responses, while a plateau remaining after a high K+ jump was not blocked by Ca2+ removal immediately after the K+ jump. Thus Cs+ loading and decreased K+ concentration in autaptic terminals by a conditioning depolarizing current selectively sensitize the terminals to a subthreshold high K+ jump for depolarization to activate synchronous or asynchronous transmitter release. Nicardipine (5–10 μM) blocked type-1 and -2 responses but not type-3 responses, while ω-conotoxin (10 μM) blocked all the types of K10 response in the presence of nicardipine. Increasing the interval of high K+ jumps biphasically increased the magnitude of K10 response, preferentially in the postjump fraction reflecting purely the asynchronous activation of exocytotic machinery, and decreased the reduction of miniature postsynaptic current frequency after a K10 response. These results suggest the roles of N(P/Q)-type Ca2+ channels in synchronous exocytosis at the terminals, L-type Ca2+ channels in initiating a Ca2+ action potential at the parent axon and both types in asynchronous exocytosis and also suggest the different releasable pools of transmitter for two modes of exocytosis in cultured hippocampal neurons.

Rate Coding and Spike-Time Variability in Cortical Neurons With Two Types of Threshold Dynamics

2006 ◽  
Vol 95 (4) ◽  
pp. 2650-2663 ◽  
Author(s):  
T. Tateno ◽  
H.P.C. Robinson
Keyword(s):  
Cortical Neurons ◽  
Threshold Dynamics ◽  
Optimum Level ◽  
Spike Time ◽  
Spike Generation ◽  
Shunting Inhibition ◽  
Rate Coding

Neurons and dynamical models of spike generation display two different classes of threshold behavior: type 1 [firing frequency vs. current ( f– I) relationship is continuous at threshold] and type 2 (discontinuous f– I). With steady current or conductance stimulation, regular-spiking (RS) pyramidal neurons and fast-spiking (FS) inhibitory interneurons in layer 2/3 of somatosensory cortex exhibit type 1 and type 2 threshold behaviors, respectively. We compared the postsynaptic firing variability of type 1 RS and type 2 FS cells, during naturalistic, fluctuating conductance input. In RS neurons, increasing the level of independently random, shunting inhibition caused a monotonic increase in spike reliability, whereas in FS interneurons, there was an optimum level of shunting inhibition for achieving the most reliable spike generation and the most precise spike-time encoding. This was observed over a range of different degrees of synchrony, or correlation, in the input. RS cells displayed a progressive rise in spike jitter during natural-like transient burst inputs, whereas for FS cells, jitter was mostly kept low. Furthermore, RS cells showed encoding of the input level in the spike shape, whereas FS cells did not. These differences between the two cell types are consistent with a role of RS neurons as rate-coding integrators, and a role of FS neurons as resonators controlling the coherence of synchronous firing.

scholarly journals Characteristics of Five Types of K+ Channel in Cultured Locust Muscle

1990 ◽  
Vol 154 (1) ◽  
pp. 45-65
Author(s):  
P. N. Usherwood
Keyword(s):  
Single Channel ◽  
Inward Rectifier ◽  
Resting Potential ◽  
K Channel ◽  
Chord Conductance ◽  
Outward Currents ◽  
Inward Currents

K+ channel activity in cultured locust myofibres was investigated using gigaohm patch-clamp techniques. After 2 months in vitro the myofibres had a mean resting potential of −39 ± 7 mV (±S.D., 7V = 42). Five types of K+ channel were identified at this time. The majority of single-channel events recorded from cellattached patches were due to a small-conductance (type 1) and a largeconductance (type 2), inward rectifier, K+ channel. In cell-attached patches, with 180 mmoll−1 KC1 in the patch pipette, the type 1 channel had a chord conductance of 43 pS for inward currents and 8pS for outward currents; the type 2 channel had a chord conductance of 115 pS for inward currents and 29 pS for outward currents. The type 2 channel exhibited bursting kinetics, was ATP-sensitive and could be blocked by Ba2+. Two other channels (types 3 and 4) had linear conductances of 130pS and 207pS, respectively. The type 3 channel was Ca2+-sensitive. A further channel (type 5) appeared to be an inward rectifier with a conductance of 5pS. Openings of types 3, 4 and 5 channels occurred less frequently than openings of the other two channels. Types 1, 2, 3 and 4 channels possessed multiple closed and open states with non-linear gating mechanisms.

Type 2 Diabetes Overtakes Type 1 in Hispanic Girls

2008 ◽  
Vol 38 (15) ◽  
pp. 18
Author(s):  
SHERRY BOSCHERT
Keyword(s):  
Type 2 Diabetes
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