Page 249 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 14 Agents Used in Cardiac Arrhythmias 235

TABLE 14–1 Molecular and genetic basis of some cardiac arrhythmias.

Chromosome Ion Channel or
Type Involved Defective Gene Proteins Affected Result
LQT-1 11 KCNQ1 I Ks LF
LQT-2 7 KCNH2 (HERG) I Kr LF
LQT-3 3 SCN5A I Na GF
LQT-4 4 Ankyrin-B 1 LF
LQT-5 21 KCNE1 (minK) I Ks LF
LQT-6 21 KCNE2 (MiRP1) I Kr LF
LQT-7 2 17 KCNJ2 I Kir LF
LQT-8 3 12 C ACNA1c I Ca GF
SQT-1 7 KCNH2 I Kr GF
SQT-2 11 KCNQ1 I Ks GF
SQT-3 17 KCNJ2 I Kir GF
CPVT-1 4 1 hRyR2 Ryanodine receptor GF
CPVT-2 1 CASQ2 Calsequestrin LF
Sick sinus syndrome 15 or 3 HCN4 or SCN5A 5 LF
Brugada syndrome 3 SCN5A I Na LF
PCCD 3 SCN5A I Na LF
Familial atrial fibrillation 11 KCNQ1 I Ks GF
1 + + + + 2+ 2+
Ankyrins are intracellular proteins that associate with a variety of transport proteins including Na channels, Na /K -ATPase, Na , Ca exchange, and Ca release channels.
2 Also known as Andersen syndrome.
3
Also known as Timothy syndrome; multiple organ dysfunction, including autism.
2+
4 CPVT, catecholaminergic polymorphic ventricular tachycardia; mutations in intracellular ryanodine Ca release channel or the Ca buffer protein, calsequestrin, may result in
2+
2+
2+
enhanced sarcoplasmic reticulum Ca leakage or enhanced Ca release during adrenergic stimulation, causing triggered arrhythmogenesis.
5 HCN4 encodes a pacemaker current in sinoatrial nodal cells; mutations in sodium channel gene (SCN5A) cause conduction defects.
GF, gain of function; LF, loss of function; LQT, long QT syndrome; PCCD, progressive cardiac conduction disorder; SQT, short QT syndrome.

Forward impulse Retrograde
obstructed and extinguished impulse
Purkinje twig

Depressed region

A. Normal conduction B. Unidirectional block

FIGURE 14–6 Schematic diagram of a reentry circuit that might occur in small bifurcating branches of the Purkinje system where they
enter the ventricular wall. A: Normally, electrical excitation branches around the circuit, is transmitted to the ventricular branches, and becomes
extinguished at the other end of the circuit due to collision of impulses. B: An area of unidirectional block develops in one of the branches,
preventing anterograde impulse transmission at the site of block, but the retrograde impulse may be propagated through the site of block if
the impulse finds excitable tissue; that is, the refractory period is shorter than the conduction time. This impulse then reexcites tissue it had
previously passed through, and a reentry arrhythmia is established.