scholarly journals CaMKII Modulates the Cardiac Transient Outward K+ Current through its Association with Kv4 Channels in Non-Caveolar Membrane Rafts

2019 ◽  
Vol 54 (1) ◽  
pp. 27-39
Keyword(s):  
Membrane Rafts ◽  
Kv4 Channels ◽  
K Current

Modulation of Kv4 channels, key components of rat ventricular transient outward K+ current, by PKC

1997 ◽  
Vol 273 (4) ◽  
pp. H1775-H1786 ◽  
Author(s):  
Tomoe Y. Nakamura ◽  
William A. Coetzee ◽  
Eleazar Vega-Saenz De Miera ◽  
Michael Artman ◽  
Bernardo Rudy
Keyword(s):  
Outward Current ◽  
Current Evidence ◽  
Inactivation Kinetics ◽  
Transient Outward Current ◽  
Recovery From Inactivation ◽  
Kv4 Channels ◽  
K Current ◽  
Molecular Components ◽  
Kinetics Of ◽  
Pkc Activation

Current evidence suggests that members of the Kv4 subfamily may encode native cardiac transient outward current ( I to). Antisense hybrid-arrest with oligonucleotides targeted to Kv4 mRNAs specifically inhibited rat ventricular I to, supporting this hypothesis. To determine whether protein kinase C (PKC) affects I to by an action on these molecular components, we compared the effects of PKC activation on Kv4.2 and Kv4.3 currents expressed in Xenopus oocytes and rat ventricular I to. Phorbol 12-myristate 13-acetate (PMA) suppressed both Kv4.2 and Kv4.3 currents as well as native I to, but not after preincubation with PKC inhibitors (e.g., chelerythrine). An inactive stereoisomer of PMA had no effect. Phenylephrine or carbachol inhibited Kv4 currents only when coexpressed, respectively, with α1C-adrenergic or M1 muscarinic receptors (this inhibition was also prevented by chelerythrine). The voltage dependence and inactivation kinetics of Kv4.2 were unchanged by PKC, but small effects on the rates of inactivation and recovery from inactivation of native I to were observed. Thus Kv4.2 and Kv4.3 proteins are important subunits of native rat ventricular I to, and PKC appears to reduce this current by affecting the molecular components of the channels mediating I to.

scholarly journals A Role for DPPX Modulating External TEA Sensitivity of Kv4 Channels

2008 ◽  
Vol 131 (5) ◽  
pp. 455-471 ◽  
Author(s):  
Olaia Colinas ◽  
Francisco D. Pérez-Carretero ◽  
José R. López-López ◽  
M. Teresa Pérez-García
Keyword(s):  
Kinetic Properties ◽  
Scaffolding Proteins ◽  
Physiological Properties ◽  
Kv4 Channels ◽  
Voltage Dependent ◽  
Oxygen Sensitive ◽  
K Current ◽  
Chemoreceptor Cells ◽  
Heterologous Expression Systems ◽  
Kinetic Effects

Shal-type (Kv4) channels are expressed in a large variety of tissues, where they contribute to transient voltage-dependent K+ currents. Kv4 are the molecular correlate of the A-type current of neurons (ISA), the fast component of ITO current in the heart, and also of the oxygen-sensitive K+ current (KO2) in rabbit carotid body (CB) chemoreceptor cells. The enormous degree of variability in the physiological properties of Kv4-mediated currents can be attributable to the complexity of their regulation together with the large number of ancillary subunits and scaffolding proteins that associate with Kv4 proteins to modify their trafficking and their kinetic properties. Among those, KChIPs and DPPX proteins have been demonstrated to be integral components of ISA and ITO currents, as their coexpression with Kv4 subunits recapitulates the kinetics of native currents. Here, we explore the presence and functional contribution of DPPX to KO2 currents in rabbit CB chemoreceptor cells by using DPPX functional knockdown with siRNA. Additionally, we investigate if the presence of DPPX endows Kv4 channels with new pharmacological properties, as we have observed anomalous tetraethylammonium (TEA) sensitivity in the native KO2 currents. DPPX association with Kv4 channels induced an increased TEA sensitivity both in heterologous expression systems and in CB chemoreceptor cells. Moreover, TEA application to Kv4-DPPX heteromultimers leads to marked kinetic effects that could be explained by an augmented closed-state inactivation. Our data suggest that DPPX proteins are integral components of KO2 currents, and that their association with Kv4 subunits modulate the pharmacological profile of the heteromultimers.

scholarly journals Auxiliary KChIP4a Suppresses A-type K+Current through Endoplasmic Reticulum (ER) Retention and Promoting Closed-state Inactivation of Kv4 Channels

2013 ◽  
Vol 288 (21) ◽  
pp. 14727-14741 ◽  
Author(s):  
Yi-Quan Tang ◽  
Ping Liang ◽  
Jingheng Zhou ◽  
Yanxin Lu ◽  
Lei Lei ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Closed State ◽  
Type K ◽  
Er Retention ◽  
Kv4 Channels ◽  
K Current

scholarly journals Gating Charge Immobilization in Kv4.2 Channels: The Basis of Closed-State Inactivation

2008 ◽  
Vol 131 (3) ◽  
pp. 257-273 ◽  
Author(s):  
Kevin Dougherty ◽  
Jose A. De Santiago-Castillo ◽  
Manuel Covarrubias
Keyword(s):  
Ionic Current ◽  
State Diagram ◽  
Clear Understanding ◽  
Gating Currents ◽  
Closed State ◽  
Gating Charge ◽  
Activation Gate ◽  
Kv4 Channels ◽  
K Current ◽  
Crucial Information

Kv4 channels mediate the somatodendritic A-type K+ current (ISA) in neurons. The availability of functional Kv4 channels is dynamically regulated by the membrane potential such that subthreshold depolarizations render Kv4 channels unavailable. The underlying process involves inactivation from closed states along the main activation pathway. Although classical inactivation mechanisms such as N- and P/C-type inactivation have been excluded, a clear understanding of closed-state inactivation in Kv4 channels has remained elusive. This is in part due to the lack of crucial information about the interactions between gating charge (Q) movement, activation, and inactivation. To overcome this limitation, we engineered a charybdotoxin (CTX)-sensitive Kv4.2 channel, which enabled us to obtain the first measurements of Kv4.2 gating currents after blocking K+ conduction with CTX (Dougherty and Covarrubias. 2006J. Gen. Physiol. 128:745–753). Here, we exploited this approach further to investigate the mechanism that links closed-state inactivation to slow Q-immobilization in Kv4 channels. The main observations revealed profound Q-immobilization at steady-state over a range of hyperpolarized voltages (−110 to −75 mV). Depolarization in this range moves <5% of the observable Q associated with activation and is insufficient to open the channels significantly. The kinetics and voltage dependence of Q-immobilization and ionic current inactivation between −153 and −47 mV are similar and independent of the channel's proximal N-terminal region (residues 2–40). A coupled state diagram of closed-state inactivation with a quasi-absorbing inactivated state explained the results from ionic and gating current experiments globally. We conclude that Q-immobilization and closed-state inactivation at hyperpolarized voltages are two manifestations of the same process in Kv4.2 channels, and propose that inactivation in the absence of N- and P/C-type mechanisms involves desensitization to voltage resulting from a slow conformational change of the voltage sensors, which renders the channel's main activation gate reluctant to open.

Membrane–cytoskeleton interactions in cholesterol-dependent domain formation

2015 ◽  
Vol 57 ◽  
pp. 177-187 ◽  
Author(s):  
Jennifer N. Byrum ◽  
William Rodgers
Keyword(s):  
Biological Properties ◽  
Membrane Rafts ◽  
Membrane Domains ◽  
Biological Functions ◽  
Membrane Cytoskeleton ◽  
Heterogeneous Structures ◽  
Integral Role ◽  
Model Cell ◽  
Actomyosin Cytoskeleton ◽  
Dependent Domain

Since the inception of the fluid mosaic model, cell membranes have come to be recognized as heterogeneous structures composed of discrete protein and lipid domains of various dimensions and biological functions. The structural and biological properties of membrane domains are represented by CDM (cholesterol-dependent membrane) domains, frequently referred to as membrane ‘rafts’. Biological functions attributed to CDMs include signal transduction. In T-cells, CDMs function in the regulation of the Src family kinase Lck (p56lck) by sequestering Lck from its activator CD45. Despite evidence of discrete CDM domains with specific functions, the mechanism by which they form and are maintained within a fluid and dynamic lipid bilayer is not completely understood. In the present chapter, we discuss recent advances showing that the actomyosin cytoskeleton has an integral role in the formation of CDM domains. Using Lck as a model, we also discuss recent findings regarding cytoskeleton-dependent CDM domain functions in protein regulation.

Sign in / Sign up

Export Citation Format

Share Document