Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 265

Delayed K + Rectifiers

Delayed K + rectifiers activate later and inactivate more slowly during the repolar-
ization than transient outward K + channels. Rapid delayed K + rectifiers have faster
activation and deactivation kinetics and more negative threshold potential than slow
delayed K + rectifiers. A third type exists, ultrarapid delayed K + rectifiers. These
3 delayed K + rectifiers underlie repolarization phase 3.
Subunits K V 11.1 and K V 7.1 are related to the rapid and slow delayed K + recti-
fiers, respectively (Table 5.12 ). K V 11.1 channel is responsible for the rapid delayed
rectifier K + current during the third phase of repolarization. It exists not only in
cardiomyocytes, but also in smooth myocytes and other cells. At negative membrane
potentials, K V 11.1 channels are in a closed state. Membrane depolarization slowly
opens the channel that is then rapidly inactivated. K V 1.5 channel underlies the
ultrarapid component of outward delayed K + rectifiers in the atrium.

5.10.4.2 Inward Rectifier Potassium Channels (K IR )

Cardiac GIRK Channel

G-protein-dependent K + inward

βγ
subunit, 98 has negative chronotropic effect and explains acetylcholine-induced
bradycardia ( i K ACh current). These channels of the sinoatrial node indeed decelerate
the pacemaker activity. Potassium flux depends on the electrochemical gradient for
K + across the sarcolemma.
GIRK channels are heterotetramers of K + inward rectifier subunits of the K IR 3
group combined in a cell-specific manner. GIRK channel of the atriomyocyte
is composed of K IR 3.1 and K IR 3.4. Each subunit has one G

rectifier (GIRK or K G ), activated by G

binding site.
The subcellular localization of GIRK channels involves PDZ domain-containing
anchoring proteins.
Cell membrane hyper- and depolarization lead to fast 99 and slow (“relax-
ation”) 100 increase and decrease in channel activity, respectively [ 478 ].
During sarcolemma repolarization, the GTPase-accelerating protein action of
regulators of G-protein signaling is inhibited by phosphatidylinositol (3,4,5)-
trisphosphate that binds to RGS4 [ 479 ]. Voltage-dependent formation of Ca 2 + -
calmodulin leads to its binding to regulators of G-protein signaling. Thereby,
Ca 2 + -calmodulin relieves the inhibition by phosphatidylinositol trisphosphate and

βγ

98 The availability of each channel subunit is dictated by G

βγ concentration, the available status

being characterized by a higher affinity for G subunit.

99 The fast channel flux is due to the blockade of outward K + motion through the channel by
intracellular Mg 2 + and polyamines. This feature is common to almost all K IR channels.
100 The slow channel flux is specific to GIRK channel. It is due to the voltage-dependent action of
regulators of G-protein signaling that accelerate the intrinsic GTP hydrolysis of the G

βγ

α

subunit.