review article

Calcium channel mechanism and target

therapeutic in the arrhythmias

Chao Jing, Shu Yi Huang

Abstract

Arrhythmias, as well as major common cardiac disease in the world, has severe

influences on patients’ life quality. Furthermore, some arrythmia can also ca

use stroke

and

other

vascular

diseases,

which

means

most

patients

with

arrhythmia

taking

life

threatening risk, influence patients life quality. As we know, ion channel, especially

calcium channel plays an important role in the arrhythmia, even in sometimes could

affect

patients

with

arrhythmia

outcomes

and

drugs

effects.

tradition

treatments

include beta blocker,calcium channel blocker, and anti- arrhythmia drugs, for instance

Ia

or

Ic

type

drugs,

in

some

conditions,

Warfarin

or

aspirin

are

used

to

prevent

ischemic stroke, above all older individual. despite, these anti-arrhythmias therapeutic

have

major

limited

,

such

in

some

patients

no

effect

and

side

effect

may

make

threatening.

researchers

now

know

that

new

mechanism

in

this

instance

use

calmodulin

（

CaM

）

and

Ca

2

?

/CaM-dependent protein kinase II

(CaMKII)

may

be as novel target therapeutic in the future, could improve patients life quality, cause

drugs make more effect and reduce side effect in the subclinical.

Key words

:arrhythmia;ion channel;target treatment

Introduction

The cardiac events that occur from the beginning of one heartbeat to the

beginning of the next are called the cardiac cycle. It consists of two parts, a

contraction and a relaxation. The cardiac cycle consists of a period of relaxation

called diastole, during which the heart fills with blood, followed by a period of

contraction called systole. The specialized conduction system is made up with atrial

and ventricular heart cells. When this system functions normally, it generates

rhythmic excitement. Disorders of cardiac rate and rhythm are referred to as

arrhythmias.

The action potential which made the cells become excited is composed of both

depolarization and repolarization waves and it is divided into five periods. The rise in

action potential (phase 0) is caused by rapidly increasing Na current carried by

voltage-gated Na channels. Na current falls rapidly because voltage-gated Na

channels are inactivated. When Na current is inhibited, the excitatory transmission

becomes slow. When a severe suppression comes, it can be transformed into slow

action potentials. And that’s the main feature of the traditional Class I antiarrhythmic

drugs, to inhibit Na current. In phase 2, due to the presence of L-type calcium current,

calcium slow and sustained influx led to the formation of the plateau. During phase 2,

with the presence of L-type calcium current, a large quantity of both calcium flows

through these channels to the interior of the cardiac muscle fiber, and this maintains a

prolonged period of depolarization, causing the plateau which accounts for the

prolonged action potential. In phase 4, since the ventricular action potential remains

stable, it was known as the resting membrane potential.

In the united stated, cardiac arrhythmias are leading cause of morbidity and

mortality more than 300,000 individuals suddenly cardiac death every year

[1]

. and also

in the Asia, sudden cardiac death occurs approximately 40 cases

[2]

. such as Atrial

fibrillation (AF) , ventricular fibrillation (VF) ,and catecholaminergic polymorphic

ventricular tachycardia (CPVT) , not only affect patients life quality worse, but also

had life threatening risk factors.

Most of researches about arrhythmia mechanisms ague that inherited or

acquired dysfunction of cardiac ion channels could lead to disorder

[3]

, especially

calcium channel and RyR2 mutation.

On the one hand, use the positional cloning candidate gene approach suggest

that RyR2 mutation may association with calcium release in cardiac sarcoplasmic

reticulum

[4]

.

On the other hand, RyR2 activated by calcium transiently enters the cell through

L-type calcium channel in the depolarization of the cardiac myocyte could play a

important role in abnormal intracellular calcium metabolism

[5]

.

Recently, researchers found that RyR2 mutation and CaM mutation, CaMKII

could as target for major types arrhythmia, may be make new approach in the

arrhythmias treatment, and may alternative traditional therapeutic, improve patients

with arrhythmia life quality.

In the heart of the ionic mechanisms, calcium pump also plays an important

role. Calcium pump is an kind of ion pump which widely present in mammalian cells,

2

?

Ca

also known as

-ATPase. Not only in the plasma membrane, calcium pump is

also present in sarcoplasmic reticulum of muscle cells and endoplasmic reticulum of

2

?

other cells. When

Ca

level rises, it could bind to calmodulin to stimulate calcium

pump.

In this review, we clarify that calcium channel included L-type calcium,

2

?

calmodulin, and

Ca

/CaM-dependent protein kinase II effect electrical activity of

the heart mechanisms, finally, we argue that calcium channel novel target therapeutic

how make benefit in the patients with arrhythmia and future perspective.

I. Calcium channel association with arrhythmias functions

Calcium-calmodulin- dependent protein kinase II (CaMKII) not only a simple

sensor to changes in intracellular calcium, but also is a dodecamericholoenzyme from

is a multi- functional serine/theronine protein kinase with numberous

biological functions in many cell types,include the heart

[6]

.

They function components have α

-

，

β

< br>-

，

δ

-

，

and γ

- subunits. in the myocardial

cells

found

δb

and

δc

subunits

display

distinatlocalization

profiles,

may

association