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K+ K+ Ca+ Tropomyosin alpha-1 chain Tropomyosin beta chain Voltage- dependent P/Q-type calcium channel subunit alpha-1A Voltage- dependent L-type calcium channel subunit beta-1 Voltage- dependent calcium channel subunit alpha-2/delta-2 Beta-1 adrenergic receptor cAMP-dependent protein kinase type I-alpha regulatory subunit 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 Ryanodine receptor 2 Muscarinic acetylcholine receptor M2 Cardiac phospholamban Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 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 Sodium/calcium exchanger 1 cAMP-dependent protein kinase catalytic subunit alpha Inward rectifier potassium channel 2 Nifedipine Ca+ 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+ Nifedipine Ca+ Troponin Troponin G-protein signalling cascade 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 Cardiac Muscle Striated Muscle Cell Nucleus Mitochondrion Myofibril Sarcoplasmic Reticulum 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 Nifedipine is typically administered intravenously as a racemic mixture Nifedipine inhibits L-type calcium channels by binding to Cav1.2, part of their alpha-1 subunit Vascular Smooth Muscle Cell Nifedipine prevents calcium ion influx by blocking calcium channels, which prevents smooth muscle contraction and relaxes the cells, leading to lower peripheral vascular resistance i.e. lower blood pressure. Nifedipine can reduce angina, treat certain types of arrhythmia, and reduce hypertension by inhibiting calcium channels systemically and in the heart. As Nifedipine is lipophilic, it can diffuse into the cell. As well, there is some evidence that it can interact with organic cation transporters of the ABC family and alter P-glycoprotein efflux pump activity. Extracellular Space