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Mechanisms Underlying the Frequency Dependence of Contraction and [Ca 2+ ] i Transients in Mouse Ventricular Myocytes
Author(s) -
Antoons Gudrun,
Mubagwa Kanigula,
Nevelsteen Ines,
Sipido Karin R.
Publication year - 2002
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.2002.025619
Subject(s) - stimulation , caffeine , contraction (grammar) , myocyte , medicine , chemistry , endocrinology , biology
In most mammalian species force of contraction of cardiac muscle increases with increasing rate of stimulation, i.e. a positive force‐frequency relationship. In single mouse ventricular cells, both positive and negative relationships have been described and little is known about the underlying mechanisms. We studied enzymatically isolated single ventricular mouse myocytes, at 30 °C. During field stimulation, amplitude of unloaded cell shortening increased with increasing frequency of stimulation ( 0.04 ± 0.01 Δ L / L 0 at 1 Hz to 0.07 ± 0.01 Δ L / L 0 at 4 Hz, n = 12, P < 0.05 ). During whole cell voltage clamp with 50 μM [K5‐fluo‐3] pip , both peak and baseline [Ca 2+ ] i increased at higher stimulation frequencies, but the net Δ[Ca 2+ ] i increased only modestly from 1.59 ± 0.08 Δ F / F 0 at 1 Hz, to 1.71 ± 0.11 Δ F / F 0 at 4 Hz ( n = 17, P < 0.05). When a 1 s pause was interposed during stimulation at 2 and 4 Hz, [Ca 2+ ] i transients were significantly larger (at 4 Hz, peak F / F 0 increased by 78 ± 2 %, n = 5). SR Ca 2+ content assessed during caffeine application, significantly increased from 91 ± 24 μmol l −1 at 1 Hz to 173 ± 20 μmol l −1 at 4 Hz ( n = 5, P < 0.05). Peak I Ca,L decreased at higher frequencies (by 28 ± 6 % at 2 Hz, and 45 ± 8 % at 4 Hz), due to slow recovery from inactivation. This loss of I Ca,L resulted in reduced fractional release. Thus, in mouse ventricular myocytes the [Ca 2+ ] i ‐frequency response depends on a balance between the increase in SR content and the loss of trigger I Ca,L . Small changes in this balance may contribute to variability in frequency‐dependent behaviour. In addition, there may be a regulation of the contractile response downstream of [Ca 2+ ] i .