Flashcards in ion channels 2 Deck (30):
1. – (Kv4.3 tetramer + KChiP2)
2. voltage-dependent inactivation
1. (HERG tetramer + miRP1)
2. “rapid” delayed rectifier
1. (KvLQT1 tetramer + minK)
2. “slow” delayed rectifier
Time-dependent cation current
1. If (or Ih)
2. (HCN tetramer)
3. Evoked by hyperpolarization
4. Na+ & K+ permeable
5. Erev ~ -30 mV
Inward Rectifier potassium currents
1. (GIRK tetramer)
2. Increased by activation of muscarinic receptors
3. slows pacemaking
1. Turning on of If
2. Activation of ICa-T
3. Deact. of IKr & IKs
HERG is an
“anti-target” tested in preclinical evaluation of new drugs
HERG is important for
duration of slow and fast APs
Reducing Ikr can cause
HERG is blocked by
in the heart, electrical activity functions to
1. Generates repetitive firing in specialized, “pacemaker” regions
2. Propagates within the myocardium and via specialized conductive pathways
3. Serves as a trigger for contraction of the myocardium
The cardiac action potential is the trigger for an
increase in the intracellular concentration of calcium ions, which, in turn, causes contraction of the myocardium.
initiate cardiac AP
slowly depolarize to threshold in the absence of extrinsic input
The rate at which a normal heart beats is controlled by
pacemaker cells in the sinoatrial node (SA node).
The SA node is a
1. cluster of small (7 μm diameter), round and spindle-shaped cells that contain few myofilaments.
cells are spontaneously active
will fire action potentials at a frequency of about 100/min
The SA node is innervated by
both sympathetic and parasympathetic axons.
Ongoing activity in the parasympathetic axons (parasympathetic tone) typically slows the rate at which cells in the SA node fire to 60-80 action potentials/min.
an action potential will spread to them from the SA node before they reach threshold on their own
Under abnormal circumstances these cells (or others, especially cells in damaged regions of the myocardium) can take over initiation of the heartbeat
Because heart rate is controlled by electrical activity of the SA node, the propagation of this activity to other regions of the heart has to occur such that
the two atria contract and relax in a coordinated fashion, that two ventricles contract and relax in a coordinated fashion, and that ventricular contraction occurs during atrial relaxation (and vice versa).
High Voltage activated (HVA) types
1. L type
L type channels include
CaV1.1, CaV1.2, CaV1.3, CaV1.4
Neuronal channels include
CaV2.1, CaV2.2, CaV2.3
Low voltage activated (LVA) types
T type, which includes: Cav3.1, 3.2, 3.3
L-type calcium channels containing CaV1.2 are predominant in
ventricular and atrial myocardium and cells of the SA and AV nodes and conductive pathways.