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K+ K+ Ca+ Voltage-gated rapid delayed rectifying potassium channel (IKr) Tropomyosin alpha-1 chain Tropomyosin beta chain Ryanodine receptor 2 Muscarinic acetylcholine receptor M2 Inward rectifier potassium channel 4 Potassium voltage-gated channel subfamily D member 3 Kv channel- interacting protein 2 Potassium voltage-gated channel subfamily A member 5 Disks large homolog 1 Potassium voltage-gated channel subfamily KQT member 1 Potassium voltage-gated channel subfamily E member 1 Potassium voltage-gated channel subfamily E member 2 ATP-binding cassette sub-family C member 8 ATP-sensitive inward rectifier potassium channel 8 ATP-sensitive inward rectifier potassium channel 11 ATP-binding cassette sub-family C member 9 Potassium channel subfamily K member 1 Sodium/calcium exchanger 1 Potassium/sodium hyperpolarization- activated cyclic nucleotide- gated channel 4 Sodium channel protein type 5 subunit alpha Beta-2- syntrophin Beta-1- syntrophin Alpha-1- syntrophin Voltage- dependent T-type calcium channel subunit alpha-1H Voltage- dependent T-type calcium channel subunit alpha-1G Voltage- dependent L-type calcium channel subunit alpha-1C Voltage- dependent calcium channel subunit alpha-2/delta-2 Voltage- dependent L-type calcium channel subunit beta-1 Sodium/calcium exchanger 1 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Inward rectifier potassium channel 2 Voltage-gated rapid delayed rectifying potassium channel (IKr) Amiodarone Ca+ K+ K+ Na+ Na+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Ca+ Ca+ Na+ Na+ Na+ Na+ K+ K+ Na+ Na+ Ca+ Ca+ Ca+ Ca+ Ca+ Na+ Na+ ATP H2O Ca+ ADP Pi Ca+ Ca+ Voltage-gated rapid delayed rectifying potassium channel (IKr) Troponin Troponin G-protein signalling cascade Muscle Contraction G protein- activated inward rectifier potassium channel 1 G protein- activated inward rectifier potassium channel 4 Potassium voltage-gated channel subfamily H member 2 Putative Dol-P- Glc:Glc(2)Man(9)GlcNAc(2)- PP-Dol alpha-1,2- glucosyltransferase T-wave Amiodarone blocks the voltage -gated rapid delayed rectifying potassium channel. K+ cannot exit the cell as quickly since the channels are blocked. ACTION POTENTIAL Time Membrane Potential (mV) Resting Potential Threshold Depolarization K+ channel blockade by amiodarone Repolarization Partial repolarization Plateau The repolarization phase of the action potential is prolonged and the action potential duration is increased, causing decreased excitability of the myocyte. P-wave QRS complex Time Electrical activity (mV) HEART RATE With amiodarone Without amiodarone The decreased excitability leads to slowing of the heart rate. The QRS duration increases as well as the QT interval. Cardiac Muscle Striated Muscle Cell Myofibril Myofibril in Cardiac Myocyte Sarcolema Sarcoplasmic Reticulum Calcium binding to troponin displaces tropomyosin from the myosin binding sites on the actin filaments Myosin, with an ADP and phosphate attached, binds to actin to form a cross bridge. Myosin performs a powerstroke, drawing the actin filaments together. Many actin filaments pulled together at the same time leads to muscle contraction. Actin Filament Myosin Filament T-Tubule Depolarization Mitochondrion Single Sarcomere Functioning Unit
Golgi Apparatus Golgi Apparatus Mitochondria Potassium Potassium Calcium ALG10B TPM1 TPM2 RYR2 CHRM2 KCNJ4 KCND3 KCNIP2 Unknown Unknown KCNQ1 KCNE1 KCNE2 ABCC8 KCNJ8 KCNJ11 Unknown KCNK1 SLC8A1 HCN4 SCN5A SNTB2 SNTB1 SNTA1 CACNA1H CACNA1G CACNA1C CACNA2D2 CACNB1 SLC8A1 ATP2A2 KCNJ2 KCNH2 Amiodarone Calcium Potassium Potassium Sodium Sodium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Calcium Calcium Sodium Sodium Sodium Sodium Potassium Potassium Sodium Sodium Calcium Calcium Calcium Calcium Calcium Sodium Sodium Adenosine triphosphate Water Calcium Adenosine diphosphate Phosphate Calcium Calcium KCNE2 Troponin Troponin G-protein signalling cascade Muscle Contraction KCNJ3 KCNJ5 KCNH2 ALG10B