A-type potassium currents in smooth muscle

Amberg, Gregory C.; Koh, Sang Don; Imaizumi, Yuji; Ohya, Susumu; Sanders, Kenton M.

doi:10.1152/ajpcell.00301.2002

Cited by 85 publications

(94 citation statements)

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“…Fast transient K ϩ currents in cardiac muscles contribute both to myocyte excitability (18) and to the fast repolarization phase of the cardiac action potential (2,8,19,20). Finally, the pharmacological block of channels that carry fast transient currents in gastrointestinal smooth muscle in mice supports the conclusion that the window currents carried by these channels contribute to the resting membrane potential and cellular excitability of smooth muscle (21,22).…”

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confidence: 69%

Mutant Analysis of the Shal (Kv4) Voltage-gated Fast Transient K+ Channel in Caenorhabditis elegans

Fawcett

Santi

Butler

et al. 2006

Journal of Biological Chemistry

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. We show that Shal channels also play a role as the predominant transient outward current in Caenorhabditis elegans muscle. Green fluorescent protein promoter experiments also revealed SHL-1 expression in a subset of neurons as well as in C. elegans body wall muscle and in male-specific diagonal muscles. The shl-1 (ok1168) null mutant removed all fast transient outward current from muscle cells. SHL-1 currents strongly resembled Shal currents in other species except that they were active in a more depolarized voltage range. We also determined that the remaining delayed-rectifier current in cultured myocytes was carried by the Shaker ortholog SHK-1. In shl-1 (ok1168) mutants there was a significant compensatory increase in the SHK-1 current. Male shl-1 (ok1168) animals exhibited reduced mating efficiency resulting from an apparent difficulty in locating the hermaphrodite vulva. SHL-1 channels are apparently important in fine-tuning complex behaviors, such as mating, that play a crucial role in the survival and propagation of the species.2 channels are key regulators of membrane excitability. Based on their inactivation kinetics, Kv currents can loosely be divided into two categories as follows: noninactivating or slowly inactivating K ϩ currents, and rapidly inactivating transient currents also known as "A-type" currents. A-type currents were first described in molluscan neurons by Hagiwara et al. (3) and later by Connor and Stevens (4), Neher (5), and Thompson (6). Classical A-type currents (I A ) are voltage-dependent, Ca 2ϩ -independent K ϩ currents that undergo rapid activation and inactivation. The classical A-type currents activate at subthreshold voltages and recover from inactivation quickly compared with other Kv currents. They are also characterized by strong steady-state voltagedependent inactivation. Repolarization to potentials negative to Ϫ50 mV is typically required to restore channel availability. A-type currents have a widespread distribution and are abundantly expressed in neurons and cardiac and smooth muscle cells, where they are thought to play many important physiological roles (2, 7-11).Connor and Stevens (12) proposed that the I A may determine the interspike interval in repetitively firing neurons. Studies in cerebellar granule cells demonstrated a role for I A in determining the latency to first spike (13). I A has also been demonstrated to limit the back propagation of action potentials into the dendritic arbor (14), to impact long term potentiation in CA1 hippocampal neurons (15), to affect neuronal excitability in the visual cortex (16), and to modulate compartmentalization of membrane excitability in distal dendritic spines (17). Fast transient K ϩ currents in cardiac muscles contribute both to myocyte excitability (18) and to the fast repolarization phase of the cardiac action potential (2,8,19,20). Finally, the pharmacological block of channels that carry fast transient currents in gastrointestinal smooth muscle in mice supports the conclusion that the window currents carried by ...

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confidence: 69%

Mutant Analysis of the Shal (Kv4) Voltage-gated Fast Transient K+ Channel in Caenorhabditis elegans

Fawcett

Santi

Butler

et al. 2006

Journal of Biological Chemistry

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“…ϩ currents have been characterized in the vascular smooth muscles of various species, as well as genitourinary and gastrointestinal (GI) smooth muscle cells (9). While the exact function of the current in smooth muscles has yet to be clarified, it most likely plays a role in the regulation of cellular excitability.…”

Section: For a Review) A-type Kmentioning

confidence: 99%

Structure and Function of Kv4-Family Transient Potassium Channels

Birnbaum

Varga

et al. 2004

Physiological Reviews

319

360

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Shal-type (Kv4.x) K+ channels are expressed in a variety of tissue, with particularly high levels in the brain and heart. These channels are the primary subunits that contribute to transient, voltage-dependent K+ currents in the nervous system (A currents) and the heart (transient outward current). Recent studies have revealed an enormous degree of complexity in the regulation of these channels. In this review, we describe the surprisingly large number of ancillary subunits and scaffolding proteins that can interact with the primary subunits, resulting in alterations in channel trafficking and kinetic properties. Furthermore, we discuss posttranslational modification of Kv4.x channel function with an emphasis on the role of kinase modulation of these channels in regulating membrane properties. This concept is especially intriguing as Kv4.2 channels may integrate a variety of intracellular signaling cascades into a coordinated output that dynamically modulates membrane excitability. Finally, the pathophysiology that may arise from dysregulation of these channels is also reviewed.

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“…Inactivation of I A is of the order of a second [Hille, 2001], so these channels are also likely involved in part in the maintenance of the slow wave plateau phase [Barajas-Lopez et al 1989]. In the GI tract, the locations and precise isoforms are variable, but there is good evidence that the K V 4 [Amberg et al 2003], K V 3 [Ohya et al 1997] families of channels are responsible for A-type current in the SMCs and perhaps ICCs [Parsons and Huizinga, 2010]. K V 4 channels have especially diverse structures and make connections with an assortment of intracellular regulators, which significantly customize their behavior [Birnbaum et al 2004].…”

Section: Nonselective Cation Channelsmentioning

confidence: 99%

Targeting ion channels for the treatment of gastrointestinal motility disorders

Beyder

Farrugia

2011

Therap Adv Gastroenterol

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Gastrointestinal (GI) functional and motility disorders are highly prevalent and responsible for long-term morbidity and sometimes mortality in the affected patients. It is estimated that one in three persons has a GI functional or motility disorder. However, diagnosis and treatment of these widespread conditions remains challenging. This partly stems from the multisystem pathophysiology, including processing abnormalities in the central and peripheral (enteric) nervous systems and motor dysfunction in the GI wall. Interstitial cells of Cajal (ICCs) are central to the generation and propagation of the cyclical electrical activity and smooth muscle cells (SMCs) are responsible for electromechanical coupling. In these and other excitable cells voltage-sensitive ion channels (VSICs) are the main molecular units that generate and regulate electrical activity. Thus, VSICs are potential targets for intervention in GI motility disorders. Research in this area has flourished with advances in the experimental methods in molecular and structural biology and electrophysiology. However, our understanding of the molecular mechanisms responsible for the complex and variable electrical behavior of ICCs and SMCs remains incomplete. In this review, we focus on the slow waves and action potentials in ICCs and SMCs. We describe the constituent VSICs, which include voltagegated sodium (Na V ), calcium (Ca V ), potassium (K V , K Ca ), chloride (Cl -) and nonselective ion channels (transient receptor potentials [TRPs]). VSICs have significant structural homology and common functional mechanisms. We outline the approaches and limitations and provide examples of targeting VSICs at the pores, voltage sensors and alternatively spliced sites. Rational drug design can come from an integrated view of the structure and mechanisms of gating and activation by voltage or mechanical stress.Keywords: functional GI, GI motility, ion channel, voltage gated ion channel, potassium voltage gated ion channel, sodium voltage gated ion channel, calcium voltage gated ion channel, chloride channelGastrointestinal functional and motility disorders Gastrointestinal (GI) functional and motility disorders are common and commonly morbid. In the broadest sense, GI functional and motility disorders refer to a group of disorders whose symptomatology is related to motor, sensory or even secretory function of the GI tract. The term 'functional' refers to the subgroup of disorders that do not yet have a well-defined pathophysiology. This broad definition means that the symptoms are nonspecific and include nausea, vomiting, bloating, abdominal discomfort or pain, constipation or diarrhea. Some of the most common motility disorders encountered in practice are achalasia, gastroparesis, intestinal pseudo-obstruction and slow transit constipation. Common functional GI disorders such as functional dyspepsia and irritable bowel syndrome (IBS) are highly prevalent in the community. For example, IBS has an estimated prevalence of 15-22% in Western society and by it...

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A-type potassium currents in smooth muscle

Cited by 85 publications

References 124 publications

Mutant Analysis of the Shal (Kv4) Voltage-gated Fast Transient K+ Channel in Caenorhabditis elegans

Mutant Analysis of the Shal (Kv4) Voltage-gated Fast Transient K+ Channel in Caenorhabditis elegans

Structure and Function of Kv4-Family Transient Potassium Channels

Targeting ion channels for the treatment of gastrointestinal motility disorders

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