Effect of input resistance voltage dependency on DC estimate of membrane capacitance in cardiac myocytes
Massimiliano Zaniboni 1*, Francesca Cacciani 1 and Maria Groppi 1
1 University of Parma
* To whom correspondence should be addressed. E-mail: zaniboni{at}biol.unipr.it.
Submitted on March 15, 2005
Revised on April 11, 2005
Accepted on 22 June 2005
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Abstract |
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The measure of membrane capacitance (Cm) in cardiac myocytes is of primary importance as an index of their size in physiological and pathological conditions, and for the understanding of their excitability. Although a plethora of very accurate methods has been developed to access Cm value in single cells, cardiac electrophysiologists still use, in the majority of laboratories, classical DC techniques as they have been established in the early days of cardiac cellular electrophysiology. These techniques are based on the assumption that cardiac membrane resistance (Rm) is constant, or changes negligibly, in a narrow potential range around resting potential. Using patch clamp whole cell recordings, both in current clamp and voltage clamp conditions, and numerical simulations, we document here the voltage dependency of Rm, up to -45% of its resting value for 10 mV hyperpolarization, in resting rat ventricular myocytes. We show how this dependency makes classical protocols to misestimate Cm in a voltage-dependent manner (up to 20% errors) which can dramatically affect Cm-based calculations on cell size and on intracellular ion dynamics. We develop a simple 'mechanistic' model to fit experimental data and obtain voltage-independent estimates of Cm, and we show that accurate estimates can be extrapolated also from the classical approach.
Key Words:
cardiac myocytes, cell size, current clamp, input resistance, membrane capacitance, voltage clamp
