Na+ current and Ca2+ release from the sarcoplasmic reticulum during action potentials in guinea-pig ventricular myocytes. 1995

K R Sipido, and E Carmeliet, and A Pappano
Laboratory of Physiology, University of Leuven, Belgium.

1. Ca2+ release from the sarcoplasmic reticulum (SR) was examined in enzymatically isolated single guinea-pig ventricular myocytes by monitoring [Ca2+]i with fura-2 during whole-cell recording of action potentials at room temperature (23-25 degrees C). Modulation of Ca2+ release by the Na+ current (INa) was studied by manipulating Na+ influx through the Na+ channel. 2. For a comparable Ca2+ loading of the SR, brief hyperpolarizing currents applied at the peak of the action potential increased Ca2+ release, while depolarizing pulses had the opposite effect. Similar currents applied before the action potential did not affect Ca2+ release. 3. Application of tetrodotoxin (TTX; 60 microM) moderately reduced Ca2+ release from the SR, but this effect was delayed in comparison with the immediate block of INa. An early effect of TTX was to increase Ca2+ release. 4. Replacement of Na+ with Li did not reduce Ca2+ release, but led to a progressive increase in Ca2+ release, resulting in spontaneous activity. 5. Ca2+ channel blockers (CdCl2, 100 microM; nisoldipine, 20 microM; or nifedipine, 20 microM) drastically reduced Ca2+ release from the SR. 6. Voltage clamp experiments confirmed that TTX blocked INa and its associated [Ca2+]i transient during voltage steps from -90 to -50 mV. INa and its associated [Ca2+]i transient were equally suppressed following replacement of Na+ with N-methyl-D-glucamine (NMDG+), but the [Ca2+]i transient was not suppressed following replacement of Na+ with Li+. 7. The INa-associated transient was sensitive to Ca2+ channel blockers. During steps from -50 to 0 mV, it appeared that the dihydropyridine antagonists often did not provide full block of the calcium current (ICa). 8. During current clamp stimulation at 1 Hz in the presence of TTX (60 microM), the Ca2+ content of the SR was decreased, due to the changes in action potential configuration and to changes in [Na+]i. 9. Our experiments indicate that the Ca2+ entry coupled to Na+ influx via the Na+ channel does not contribute substantially to the trigger for Ca2+ release from the SR during action potentials (23-25 degrees C). However, INa modulates Ca2+ release by affecting the Ca2+ load of the SR.

UI MeSH Term Description Entries
D008297 Male Males
D009543 Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Adalat,BAY-a-1040,Bay-1040,Cordipin,Cordipine,Corinfar,Fenigidin,Korinfar,Nifangin,Nifedipine Monohydrochloride,Nifedipine-GTIS,Procardia,Procardia XL,Vascard,BAY a 1040,BAYa1040,Bay 1040,Bay1040,Monohydrochloride, Nifedipine,Nifedipine GTIS
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D005260 Female Females
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006352 Heart Ventricles The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation. Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012519 Sarcoplasmic Reticulum A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions. Reticulum, Sarcoplasmic,Reticulums, Sarcoplasmic,Sarcoplasmic Reticulums
D012964 Sodium A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23

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