- Joined
- Mar 26, 2006
- Messages
- 967
- Reaction score
- 339
how do calcium channel blockers like verapamil cause decreases in HR... phase 4 diastolic depolarization is mediated by sodium currents and so i'm not sure how blocking calcium really affects that
calcium channel blockers
- Thread starter obiwan
- Start date
- Joined
- Nov 16, 2006
- Messages
- 321
- Reaction score
- 2
Maybe just by prolonging phase zero?
- Joined
- Jan 11, 2008
- Messages
- 175
- Reaction score
- 0
Phase 4 is Na and Ca+ channels acting to depolarize. Its actually MAINLY the Ca++ slow channel leaking Ca+ in that causes the quick depolarization of Phase 4 and Controls the SA node= heart RATE- i.e. affecting SA nodal rhythm. Calcium-channel blockers, cause bradycardia by inhibiting the slow inward Ca++ currents during phase 4 and phase 0.
At the end of repolarization, when the membrane potential is very negative (about -60 mV), ion channels open that conduct slow, inward (depolarizing) Na+ currents. These currents are abbreviated as "If". These depolarizing currents will cause the membrane potential to begin to spontaneously depolarize, initiating the Phase 4. As the membrane potential reaches about -50 mV or so, another type of channel opens. This channel is called transient or T-type Ca++ channel. As Ca++ enters the cell through these channels down its electrochemical gradient, the inward directed Ca++ currents further depolarize the cell. As the membrane continues to depolarize to about -40 mV, a second Ca++ channel opens. These are the so-called long-lasting, or L-type Ca++ channels. Opening of these channels causes more Ca++ to enter the cell and to further depolarize the cell until an action potential threshold is reached (usually between -40 and -30 mV). During Phase 4 there is also a slow decline in the outward movement of K+ as the K+ channels responsible for Phase 3 continue to close. This fall in K+ conductance (gK+) contributes to the pacemaker potential.
Phase 0 depolarization is primarily caused by increased Ca++ conductance through the L-type Ca++ channels that began to open toward the end of Phase 4. The If currents, and Ca++ currents through the T-type Ca++ channels, decline during this phase as their respective channels close. Because the movement of Ca++ through these channels into the cell is not rapid, the rate of depolarization (slope of Phase 0) is much slower than found in other cardiac cells (e.g., Purkinje cells).
Repolarization occurs (Phase 3) as K+ channels open thereby increasing the outward directed, hyperpolarizing K+ currents. At the same time, the L-type Ca++ channels close, and the inward depolarizing Ca++ currents diminish.
Lastly...this should give you more info than you need if that just confused you:
http://www.cvpharmacology.com/vasodilator/CCB.htm
Heres a nice copy and paste: "Calcium-channel blockers (CCBs) bind to L-type calcium channels located on cardiac myocytes and cardiac nodal tissue (sinoatrial and atrioventricular nodes). These channels are responsible for regulating the influx of calcium into cardiomyocytes, which in turn stimulates cardiac myocyte contraction. In cardiac nodal tissue, L-type calcium channels play an important role in pacemaker currents and in phase 0 of the action potentials. Therefore, by blocking calcium entry into the cell, CCBs decrease myocardial force generation (negative inotropy), decreased heart rate (negative chronotropy), and decrease conduction velocity within the heart (negative dromotropy particularly at the atrioventricular node). CCBs are used in treating hypertension, angina and arrhythmias."
At the end of repolarization, when the membrane potential is very negative (about -60 mV), ion channels open that conduct slow, inward (depolarizing) Na+ currents. These currents are abbreviated as "If". These depolarizing currents will cause the membrane potential to begin to spontaneously depolarize, initiating the Phase 4. As the membrane potential reaches about -50 mV or so, another type of channel opens. This channel is called transient or T-type Ca++ channel. As Ca++ enters the cell through these channels down its electrochemical gradient, the inward directed Ca++ currents further depolarize the cell. As the membrane continues to depolarize to about -40 mV, a second Ca++ channel opens. These are the so-called long-lasting, or L-type Ca++ channels. Opening of these channels causes more Ca++ to enter the cell and to further depolarize the cell until an action potential threshold is reached (usually between -40 and -30 mV). During Phase 4 there is also a slow decline in the outward movement of K+ as the K+ channels responsible for Phase 3 continue to close. This fall in K+ conductance (gK+) contributes to the pacemaker potential.
Phase 0 depolarization is primarily caused by increased Ca++ conductance through the L-type Ca++ channels that began to open toward the end of Phase 4. The If currents, and Ca++ currents through the T-type Ca++ channels, decline during this phase as their respective channels close. Because the movement of Ca++ through these channels into the cell is not rapid, the rate of depolarization (slope of Phase 0) is much slower than found in other cardiac cells (e.g., Purkinje cells).
Repolarization occurs (Phase 3) as K+ channels open thereby increasing the outward directed, hyperpolarizing K+ currents. At the same time, the L-type Ca++ channels close, and the inward depolarizing Ca++ currents diminish.
Lastly...this should give you more info than you need if that just confused you:
http://www.cvpharmacology.com/vasodilator/CCB.htm
Heres a nice copy and paste: "Calcium-channel blockers (CCBs) bind to L-type calcium channels located on cardiac myocytes and cardiac nodal tissue (sinoatrial and atrioventricular nodes). These channels are responsible for regulating the influx of calcium into cardiomyocytes, which in turn stimulates cardiac myocyte contraction. In cardiac nodal tissue, L-type calcium channels play an important role in pacemaker currents and in phase 0 of the action potentials. Therefore, by blocking calcium entry into the cell, CCBs decrease myocardial force generation (negative inotropy), decreased heart rate (negative chronotropy), and decrease conduction velocity within the heart (negative dromotropy particularly at the atrioventricular node). CCBs are used in treating hypertension, angina and arrhythmias."
