Electrical and contractile consequences of Na+ or Ca2+ gradient reduction in cultured heart cells

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Abstract

The normal electrical and contractile activity of cultured neonatal rat ventricular cells is characterized and compared to activity seen in low [Ca2+]0 and low [Na+]0 solutions. In 0 Ca2+/0.5 mm EGTA solutions electrical activity is altered: the maximum diastolic potential (m.d.p.), maximum rate of rise (+ V ̇max), and overshoot (o.s.) are reduced, while duration is increased. Low [Ca2+]0 activity is insensitive to TTX and blocked by La3+. In low [Na+]0 solutions electrical activity is generally absent; when present + V ̇max and o.s. are decreased while duration is increased. Low [Na+]0 activity is blocked by La3+. These data suggest the presence of one La3+-sensitive slow inward current channel. The absence of spontaneous electrical activity in low [Na+]0 solutions suggests an inhibition of automaticity. To determine if this inhibition is due to a reduction of the Na+ gradient, drugs which raise [Na+]i were examined. Both monensin (a Na+ ionophore) and ouabain inhibit the occurrence of spontaneous action potentials (cells respond to stimulation) indicating a dependence of pacemaker activity on a normal Na+ gradient. During Na+ gradient reduction, asynchronous subcellular contractile activity occurs independent of membrane potential fluctuation. This asynchronous activity is inhibited by La3+ or when Ca2+0 is absent, but continues in the presence of verapamil (normal activity is blocked by all three conditions). The Na+Ca2+ exchange system is unaffected by verapamil but blocked by La3+, while both these drugs block the slow inward current. These data indicate that the Na+Ca2+ exchange system can directly supply Ca2+ (independent of electrical activity at the membrane) to intracellular sites that support contractile activity.

Original languageEnglish (US)
Pages (from-to)99-110
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Volume14
Issue number2
DOIs
StatePublished - Feb 1982
Externally publishedYes

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Keywords

  • Asynchronous contractility
  • Automaticity
  • Electrogenesis
  • Heart cell culture
  • Low [Ca]
  • Low [Na]
  • Monensin
  • NaCa exchange
  • Ouabain

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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