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Adenylate cyclase type 2 Adenylate cyclase type 2 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 Ryanodine receptor 2 Tropomyosin alpha-1 chain Tropomyosin beta chain Potassium voltage-gated channel subfamily H member 2 Putative Dol-P- Glc:Glc(2)Man(9)GlcNAc(2)- PP-Dol alpha-1,2- glucosyltransferase Potassium voltage-gated channel subfamily D member 3 Kv channel- interacting protein 2 Potassium voltage-gated channel subfamily KQT member 1 Potassium voltage-gated channel subfamily E member 1 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 Inward rectifier potassium channel 2 Inward rectifier potassium channel 4 Potassium voltage-gated channel subfamily A member 5 Disks large homolog 1 G protein- activated inward rectifier potassium channel 1 G protein- activated inward rectifier potassium channel 4 Potassium channel subfamily K member 1 Potassium/sodium hyperpolarization- activated cyclic nucleotide- gated channel 4 Gβ Gγ Beta-1 adrenergic receptor Guanine nucleotide- binding protein G(s) subunit alpha isoforms short Gβ Gγ Guanine nucleotide- binding protein G(s) subunit alpha isoforms short Guanine nucleotide- binding protein G(s) subunit alpha isoforms short cAMP-dependent protein kinase catalytic subunit alpha Beta-1 adrenergic receptor Guanine nucleotide- binding protein G(s) subunit alpha isoforms short Gβ Gγ Beta-1 adrenergic receptor Epinephrine Sotalol cAMP Ca+ Sotalol Ca+ Ca+ Ca+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ Na+ K+ GTP GDP Adenosine triphosphate PPi Magnesium GDP GTP GTP Magnesium GTP Epinephrine Epinephrine Potassium voltage-gated channel subfamily E member 2 cAMP-dependent protein kinase type I-alpha regulatory subunit Troponin Troponin Ca+ +40 0 -70 Membrane Potential (mV) Time Depolarization Repolarization Hyperpolarization Action Potential Muscle Contraction T-tubule Sarcoplasmic Reticulum Sotalol inhibits the potassium voltage-gated channel subfamily H member 2 which is apart of the potassium transport out of the cell during repolarization. Inhibition leads to slower movement of potassium proloning repolarization of the cell. Slower repolarization slows the heart rate Sotalol is a competitive inhibitor of the beta 1 adrenergic receptor stopping epinephrine from binding. Inhibition stops the downstream signalling of Gs so cyclic adenosine monophosphate (cAMP) isn't produced . Cyclic adenosine monophosphate (cAMP) is responsible for the activation of many cAMP dependent proteins like protein kinase A. Because of sotalol inhbition the cAMP dependent protein kinase alpha isn't activated which therefore cannot activate the voltage dependent calcium channell. The voltage dependent calcium channels allow the influx of calcium into the cell. Sotalol stops the calcium influx. Influx of calcium activates ryanodine receptors through calcium induced calcium release to allow the efflux of stored calcium in the sarcoplasmic reticulum. Calcium is important for muscle contraction in the heart as calcium binding allows the myosin head to bind to actin creating the power stroke. Sotalol through inhibition of the beta 1 adrenergic receptor slows the rate of calcium release and therefore the contractions of the heart prolonging the QT interval Myosin unbound to actin Myosin bound to actin in powerstroke Cardiomyocyte Sotalol is absorbed through the GI tract and delivered through the blood to the muscles. Capillaries along the sarcolemma deliver the druge to cardiac tissue.
ADCY2 ADCY2 CACNA1A CACNB1 CACNA2D2 RYR2 TPM1 TPM2 KCNH2 ALG10B KCND3 KCNIP2 KCNQ1 KCNE1 ABCC8 KCNJ8 KCNJ11 Unknown KCNJ2 KCNJ4 Unknown Unknown KCNJ3 KCNJ5 KCNK1 HCN4 GNB1 GNG2 ADRB1 GNAS GNB1 GNG2 GNAS GNAS PRKACA ADRB1 GNAS GNB1 GNG2 ADRB1 Epinephrine Sotalol cAMP Calcium Sotalol Calcium Calcium Calcium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Potassium Sodium Sodium Potassium Guanosine triphosphate Guanosine diphosphate Adenosine triphosphate Pyrophosphate Guanosine diphosphate Guanosine triphosphate Guanosine triphosphate Guanosine triphosphate Epinephrine Epinephrine KCNE2 PRKAR1A Troponin Troponin Calcium
ADCY2 ADCY2 CACNA1A CACNB1 CACNA2D2 RYR2 TPM1 TPM2 KCNH2 ALG10B KCND3 KCNIP2 KCNQ1 KCNE1 ABCC8 KCNJ8 KCNJ11 KCNJ2 KCNJ4 KCNJ3 KCNJ5 KCNK1 HCN4 GNB1 GNG2 ADRB1 GNAS GNB1 GNG2 GNAS GNAS PRKACA ADRB1 GNAS GNB1 GNG2 ADRB1 Eppy Slol cAMP Ca+ Slol Ca+ Ca+ Ca+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ Na+ K+ GTP GDP ATP PPi Mg2+ GDP GTP GTP Mg2+ GTP Eppy Eppy KCNE2 PRKAR1A Troponi Troponi Ca+ +40 0 -70 Membrane Potential (mV) Time Depolarization Repolarization Hyperpolarization Action Potential Muscle Contraction T-tubule Sarcoplasmic Reticulum Sotalol inhibits the potassium voltage-gated channel subfamily H member 2 which is apart of the potassium transport out of the cell during repolarization. Inhibition leads to slower movement of potassium proloning repolarization of the cell. Slower repolarization slows the heart rate Sotalol is a competitive inhibitor of the beta 1 adrenergic receptor stopping epinephrine from binding. Inhibition stops the downstream signalling of Gs so cyclic adenosine monophosphate (cAMP) isn't produced . Cyclic adenosine monophosphate (cAMP) is responsible for the activation of many cAMP dependent proteins like protein kinase A. Because of sotalol inhbition the cAMP dependent protein kinase alpha isn't activated which therefore cannot activate the voltage dependent calcium channell. The voltage dependent calcium channels allow the influx of calcium into the cell. Sotalol stops the calcium influx. Influx of calcium activates ryanodine receptors through calcium induced calcium release to allow the efflux of stored calcium in the sarcoplasmic reticulum. Calcium is important for muscle contraction in the heart as calcium binding allows the myosin head to bind to actin creating the power stroke. Sotalol through inhibition of the beta 1 adrenergic receptor slows the rate of calcium release and therefore the contractions of the heart prolonging the QT interval Myosin unbound to actin Myosin bound to actin in powerstroke Cardiomyocyte Sotalol is absorbed through the GI tract and delivered through the blood to the muscles. Capillaries along the sarcolemma deliver the druge to cardiac tissue.
ADCY2 ADCY2 CACNA1A CACNB1 CACNA2D2 RYR2 TPM1 TPM2 KCNH2 ALG10B KCND3 KCNIP2 KCNQ1 KCNE1 ABCC8 KCNJ8 KCNJ11 KCNJ2 KCNJ4 KCNJ3 KCNJ5 KCNK1 HCN4 GNB1 GNG2 ADRB1 GNAS GNB1 GNG2 GNAS GNAS PRKACA ADRB1 GNAS GNB1 GNG2 ADRB1 Eppy Slol cAMP Ca2+ Slol Ca2+ Ca2+ Ca2+ K+ K+ K+ K+ K+ K+ K+ K+ K+ Na+ Na+ K+ GTP GDP ATP Ppi GDP GTP GTP GTP Eppy Eppy KCNE2 PRKAR1A Troponi Troponi Ca2+