What is a Voltage Clamp?
An electrophysiology technique to control (or keep constant) an excitable cell's transmembrane voltage & measure the transmembrane current required to do so.
What is a Current Clamp?
An electrophysiology technique to apply a constant or time-varying current to an excitable cell & measure the resulting change in its transmembrane voltage.
Why would a Voltage Clamp be used?
- To measure ion currents: informs about number of open ion channels & their conductance
e.g 1. Measure effects of drugs on ion currents
e.g 2. Estimate contribution of different ion currents to cardiac action potential
- To control key variable affecting ion channel gating: voltage
Why would a Current Clamp be used?
- To measure transmembrane voltages
e.g 1. Measure voltage changes when mimicking current produced by synaptic input
e.g 2. Record cardiac action potential and effects of ion channel blockers
Why measure cardiac action potentials & the ion currents which produce them?
- Physiological study
Pathophysiological study e.g cardiac arrhythmia ventricular fibrillation is often fatal. Electrophysiological mechanisms of VF are influenced by AP characteristics & thus ion currents
Pharmacological study e.g how might drugs be anti- or pro-arrhythmic?
Computer modelling: provide real experimental data to aid mathematical simulation of highly complex nature of cardiac electrical activity
What are the 3 mechanisms of arrhythmias?
Abnormal Automaticity - Favoured by e.g ß-AR stimulation
Delayed Afterdepolarisation - Favoured by e.g Intracellular calcium overload
Early Afterdepolarisation - Favoured by e.g action potential prolongation
During electrophysiological mechanisms of atrial & ventricular arrhythmias, what causes reentry?
What is reentry during atrial & ventricular arrhythmias favoured by?
- Premature beats
- Spatial heterogeneity
- Myocardial size increase
- ERP-shortening (Effective Refractory Period)
How is Reentry Circuit Size (wavelength) measured?
RCS = Conduction Velocity x ERP
What is Ohms Law?
V = I x R
What is the formula for the Nernst equation?
(Electrochemical diffusion potential)
E = RT/zF x ln([ion outside]/[ion inside])
R=Universal gas constant
z=Valency of Ion
What is ion selectivity due to?
Channel 2° and 3° structure