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Contractions in guinea‐pig ventricular myocytes triggered by a calcium‐release mechanism separate from Na+ and L‐currents.
Author(s) -
Ferrier G R,
Howlett S E
Publication year - 1995
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1995.sp020651
Subject(s) - depolarization , ryanodine receptor , chemistry , contraction (grammar) , biophysics , tetrodotoxin , extracellular , membrane potential , verapamil , calcium , medicine , nifedipine , voltage clamp , voltage dependent calcium channel , intracellular , biology , biochemistry , organic chemistry
1. Unloaded cell shortening and membrane currents were examined in isolated guinea‐pig ventricular myocytes at 37 degrees C using video edge detection and single‐electrode voltage clamp. 2. Inward Na+ currents were eliminated by lidocaine, tetrodotoxin, replacement of extracellular Na+ with choline chloride or sucrose, or by voltage inactivation of Na+ channels. In the absence of Na+ current, the threshold for contraction was approximately ‐50 or ‐55 mV. 3. Verapamil (5 microM) and nifedipine (2 microM) failed to inhibit contractions at negative membrane potentials when positive conditioning pulses were used to maintain intracellular Ca2+ stores via Na(+)‐Ca2+ exchange. In contrast, 200 microM Ni2+ inhibited these contractions. 4. Contractions were abolished when the extracellular solution was nominally Ca2+ free. However, contractions were restored by as little as 50 microM extracellular Ca2+. 5. Ryanodine (30 nM) completely abolished contractions initiated by depolarizing steps from ‐65 to ‐40 mV, but had minimal effects on contractions initiated by depolarizing steps from ‐40 to +5 mV. Subtraction of contraction‐voltage relations determined in the presence of ryanodine from control relations revealed a ryanodine‐sensitive component of contraction. This component activated at ‐55 mV and reached a plateau near ‐25 mV. 6. The amplitudes of contractions initiated by depolarizing steps from ‐40 mV were directly proportional to the magnitude of Ca2+ current (ICa). In contrast, contractions initiated by steps from either ‐55 or ‐65 mV were not proportional to ICa. These contractions appeared at potentials negative to the threshold for L‐type Ca2+ current, increased to a plateau at more positive potentials and did not decrease at potentials at which ICa decreased. 7. Subtraction of the contraction‐voltage relationship determined from a membrane potential of ‐40 mV from that at ‐55 mV revealed a component of contraction with a negative activation threshold whose amplitude was not proportional to inward current. The shape of this relationship was virtually identical to that of the ryanodine‐sensitive component of contraction. 8. This study identifies a component of contraction associated with Ca2+ release from sarcoplasmic reticulum (SR) which can be separated from other mechanisms of contraction on the basis of membrane potential. Our observations suggest that this voltage‐dependent release mechanism is a true trigger mechanism which activates a portion of cardiac contraction which is attributable to SR Ca2+ release.