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Comparison of ultra‐slow, voltage‐dependent inactivation of the cardiac L‐type Ca2+ channel with Ca2+ or Ba2+ as the charge carrier in ferret ventricular myocytes

The whole‐cell patch clamp technique was used to investigate the effect of different charge carriers upon ultra‐slow voltage‐dependent inactivation of L‐type Ca2+ channel current in ferret ventricular myocytes at 37 degrees C. Intracellular Ca2+ was buffered with 10 mM EGTA and the membrane potential held at ‐40 mV. With Ba2+ as the charge carrier, the L‐type current decayed throughout 20 s pulses to 0 mV as a result of ultra‐slow voltage‐dependent inactivation. In contrast, with Ca2+ as the charge carrier, there was no such slow decay of the current as the current decayed almost completely in the first approximately 100 ms as a result of Ca(2+)‐dependent inactivation. However, with Ca2+ as the charge carrier it is still possible that ultra‐slow voltage‐dependent inactivation occurs. A conditioning‐test pulse protocol and a second protocol were used to test for the development of ultra‐slow inactivation during 20 or 30 s pulses to 0 mV with Ca2+ as the charge carrier. Ultra‐slow inactivation did occur and it was qualitatively similar to that with Ba2+ as the charge carrier. The onset of ultra‐slow inactivation with Ca2+ as the charge carrier could be described by the sum of two exponentials with time constants of 0.3 and 6.7 s. Recovery from ultra‐slow inactivation with Ca2+ as the charge carrier was also measured with a conditioning‐test pulse protocol and was best described by the sum of two exponentials with time constants of 0.5 and 6.2 s. We conclude that ultra‐slow inactivation of the L‐type current does occur with the physiological charge carrier, Ca2+, but it is normally masked by Ca(2+)‐dependent inactivation.