The cellular force‐frequency response in ventricular myocytes from the varanid lizard, Varanus exanthematicus

Abstract

To investigate the cellular mechanisms underlying the negative force‐frequency relationship in the ventricle of the varanid lizard, we measured sarcomere and cell shortening, intracellular Ca2+ ([Ca2+]i), action potentials (APs) and K+ currents in isolated ventricular myocytes. Experiments were conducted between 0.2–1.0 Hz, which spans the physiological range of heart rates at 20–22°C for this species. As frequency increased, diastolic length, percent change in sarcomere length and relaxation time decreased significantly. Shortening velocity was unchanged. The rate of rise of [Ca2+]i increased, [Ca2+]i transient amplitude decreased, and diastolic [Ca2+]i increased. The first order time constant of the [Ca2+]i transient decay decreased at higher frequencies, indicating frequency dependent acceleration of relaxation, then leveled out and did not change above 0.5 Hz. The AP rate of rise was unaffected, but the AP duration (APD) decreased with increasing frequency. Peak depolarization was only significantly decreased at 1.0 Hz. The decrease in APD was not due to changes in IKr or Ito. Our results suggest that a negative FFR in varanid lizard ventricle is caused by decreased amplitude of the [Ca2+]i transient with an increase in diastolic [Ca2+]i, leading to incomplete relaxation between beats at high frequencies. This coincides with shortened action potential duration (APD) at higher frequencies.