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jknell
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Fast Fibers Location
- Atrial myocytes
- Ventricular myocytes
- Purkinje Fibers
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Fast Fiber: phase 0
- Fast inward Na+ current (INa+)
- slight outward IKir
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Fast Fiber: Phase 1
- termination of INa+
- Transient activation of outward K+ channels ITO
- -small repolarization
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Fast Fiber: Phase 2
- -Slow inward Ca Channels via L type Ca channels (activated in phase 0 and are slowly inactivated) ICa-L
- -balanced by ourtward K+ currents
- -IKir (small)
- -IKv (delayed rectifier channels)
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Slow inward Ca current
- -Ca bind TnC
- -triggers CICR from SR
- Can be regulated by ANS:
- 1. ACh: M2 negative inotropic effect
- 2. NE: b1 positive inotropic effect
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Fast Fiber: Phase 3
- -Termination of ICa-L (inactivation)
- -Outward K+ currents:
- -IKv and IKir (now larger)
determines APD
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Slow Fiber: Phase 0
- -decreased slope and amplitude compared to Fast Fiber
- -no INa
- -instead ICa-L responsible for depolarization
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Slow Fiber: Phase 2
ionic events similar to fast AP
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Slow Fiber: Phase 3
ionic events similar to fast AP
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Major Determinants of Conduction Velocity
- 1. Fiber diameter (increase D causes increased CV)
- 2. Phase 0 slope and amplitude
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Interventions with Positive Dromotropic Effects in slow fibers
-increase I Ca-L
- 1. NE/E (beta 1)
- 2. b1 agonists
- 3. mAChR antagonists (block M2)
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Interventions with Negative Dromotropic Effects in slow fibers
-decrease I Ca-L
- 1. ACh (M2)
- 2. b1 antagonists
- 3. Ca channel blockers
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Interventions with Negative Dromotropic Effects in Fast fibers
-decrease I Na
- 1. Class I antiarrhythmics (block Fast Na+ channels)
- 2. Hyperkalemia (make RMP less negative)
- 3. myocardial injury (make RMP less negative)
- 4. gradual depolarization (channels inactivate before)
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Determinants of Firing Rate
- 1. Automaticity
- 2. Threshold potential
- 3. APD
- 4. Maximum Diastolic Potential (Vm at start of phase 4)
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Automaticity
- -pacemaker potential
- -steady depolarization during phase 4
- -occurs in: SA, AV and Purkinje
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Overdrive Suppression
- when a pacemaker cell is driven at a faster rate than it's intrinsic rate it's automaticity is suppressed
- (w/o Purkinje cells would be slow, and gradual depol would inactivate Na channels)
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Automaticity Mechanism
- 1. Membrane clock
- -membrane ion channels that cause repolarization of pacemaker cells activating HCN channels
- 2. HCN channels (funny channels)
- -non-specific cation channels activated by hyperpolarization
I f
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Interventions to Change Firing Rate
- 1. ACh (M2 increases IK-Ach, decreases ICa-L and decreases If ) decreases phase 4 slope
- 2. NE/EPI (b1 increases ICa-L, increases If) increases phase 4 slope
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Phase 4 slope
=automaticity
-determines firing rate
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Phase 0 Slope
-determines conduction velocity
- -Slow fibers: slow inward Ca
- -Fast fibers: fast inward Na
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Phase 3 slope
-determines APD
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