Activation of contraction in cat ventricular myocytes: effects of low Cd(2+) concentration and temperature.
The effects of Cd(2+) (20 microM) and different bath temperatures were used to study the contributions of two separate triggering mechanisms, L-type Ca(2+) current (I(Ca)) and reverse mode Na(+)/Ca(2+) exchange, to excitation-contraction (E-C) coupling in cat ventricular myocytes. Ionic currents and cell shortening were studied with patch pipettes filled with K(+)-containing internal solution and discontinuous ("switch") voltage clamp. Superfusion with Cd(2+) blocked cell shortening that closely mirrored the block of I(Ca); the voltage dependence of Cd(2+)-induced reduction in contraction was bell-shaped, displaying minima at test potentials below -10 mV and above +50 mV and a maximum at about +20 mV. Cd(2+)-insensitive cell shortening was blocked by ryanodine (10 microM) and Ni(2+) (4-5 mM). When an action potential was used as the command waveform for the voltage clamp (action potential clamp), Cd(2+) reduced contraction to approximately 60 +/- 7% of control cell shortening (n = 7). The remaining contraction was blocked by ryanodine and Ni(2+). Superfusion with nifedipine (10 microM) caused nearly identical effects to Cd(2+). The voltage dependence of contraction was sigmoidal at temperatures above 34 degrees C but bell-shaped below 30 degrees C. When Cd(2+) was added to superfusate, contraction was abolished at 25 degrees C (to 6 +/- 3% of control) but reduced only modestly at 34 degrees C (to 65 +/- 13% of control, test potential +10 mV, n = 4, P < 0.01). These results indicate that 1) there is a component of contraction that is sensitive to I(Ca) antagonists, and the block is equivalent with either organic or inorganic antagonists; 2) the contribution of Na(+)/Ca(2+) exchange to triggering of contraction under our experimental conditions is fairly linear throughout the entire voltage range tested; 3) the contribution of I(Ca) is superimposed on this background component contributed by the Na(+)/Ca(2+) exchanger; and 4) triggering via the exchanger is temperature-dependent, providing a major contribution at physiological temperatures but failing at temperatures below 30 degrees C in a nearly all-or-none fashion.
Wasserstrom
J A
JA
Department of Medicine, Division of Cardiology, Feinberg Cardiovascular Research Institute, Northwestern University Medical School, Chicago, Illinois, 60611, USA. ja-wasserstrom@nwu.edu
Vites
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D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002415:Cats; D005260:Female; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D009206:Myocardium / Q000166:cytology; D009543:Nifedipine / Q000494:pharmacology; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013696:Temperature; D016276:Ventricular Function / Q000187:drug effects* / Q000502:physiology*
D002121:Calcium Channel Blockers; D002104:Cadmium; D009543:Nifedipine; D002118:Calcium