Maximal Ca2+-activated force elicited by tetanization of ferret papillary muscle and whole heart: mechanism and characteristics of steady contractile activation in intact myocardium.
Rapid (8-12 Hz) stimulation of intact heart muscle treated with ryanodine results in steady contractile activation known as tetanus, the amplitude of which can be graded by changing extracellular Ca2+ concentration ([Ca2+]o). The mechanism of the sustained force generation was explored in ferret papillary muscles by measuring membrane potential and by determining the responsiveness of force and intracellular free Ca2+ concentration ([Ca2+]i, estimated with aequorin) to dihydropyridine Ca channel ligands. Membrane potential during tetani ranged from -25 to -60 mV, suggesting that fast or slow Ca channels, or Na-Ca exchange, might be mediating Ca2+ entry. Dihydropyridine effects indicated that slow Ca channels play a predominant role: The agonist Bay K 8644 (0.3-1 microM) increased force and aequorin luminescence, whereas the antagonist nitrendipine (1-30 microM) abolished the tetanus. Under conditions analogous to those in the papillary muscle experiments, tetani were produced in whole Langendorff-perfused ferret hearts following exposure to ryanodine. Contraction saturated as a function of [Ca2+]o in both papillary muscles and whole hearts; i.e., as [Ca2+]o was increased above 10 mM, no further increase in force or pressure generation occurred. In contrast, aequorin luminescence measured in the papillary muscles showed no such saturation. Thus, maximal Ca2+-activated force (or pressure) was achieved during tetani at [Ca2+]o greater than or equal to 10 mM. Calculations of wall stress during tetani in whole heart (15 mM [Ca2+]o) agree well with direct measurements of maximal tension in papillary muscles (5.84 g/mm2 vs. 6.41 g/mm2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002335:Carnivora / Q000502:physiology*; D005289:Ferrets / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D007473:Ion Channels / Q000502:physiology*; D008564:Membrane Potentials; D009200:Myocardial Contraction; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D012433:Ryanodine / Q000494:pharmacology; D013268:Stimulation, Chemical
D007473:Ion Channels; D012433:Ryanodine; D002118:Calcium