Ca(2+) influx through Ca(2+) channels in rabbit ventricular myocytes during action potential clamp: influence of temperature

Circ Res. 1999 Sep 17;85(6):e7-e16. doi: 10.1161/01.res.85.6.e7.

Abstract

Ca(2+) influx via Ca(2+) current (I(Ca)) during the action potential (AP) was determined at 25 degrees C and 35 degrees C in isolated rabbit ventricular myocytes using AP clamp. Contaminating currents through Na(+) and K(+) channels were eliminated by using Na(+)- and K(+)-free solutions, respectively. DIDS (0.2 mmol/L) was used to block Ca(2+)-activated chloride current (I(Cl(Ca))). When the sarcoplasmic reticulum (SR) was depleted of Ca(2+) by preexposure to 10 mmol/L caffeine, total Ca(2+) entry via I(Ca) during the AP was approximately 12 micromol/L cytosol (at both 25 degrees C and 35 degrees C). Similar Ca(2+) influx at 35 degrees C and 25 degrees C resulted from a combination of higher and faster peak I(Ca), offset by more rapid I(Ca) inactivation at 35 degrees C. During repeated AP clamps, the SR gradually fills with Ca(2+), and consequent SR Ca(2+) release accelerates I(Ca) inactivation during the AP. During APs and contractions in steady state, total Ca(2+) influx via I(Ca) was reduced by approximately 50% but was again unaltered by temperature (5.6+/-0.2 micromol/L cytosol at 25 degrees C, 6.0+/-0.2 micromol/L cytosol at 35 degrees C). Thus, SR Ca(2+) release is responsible for sufficient I(Ca) inactivation to cut total Ca(2+) influx in half. However, because of the kinetic differences in I(Ca), the amount of Ca(2+) influx during the first 10 ms, which presumably triggers SR Ca(2+) release, is much greater at 35 degrees C. I(Ca) during a first pulse, given just after the SR was emptied with caffeine, was subtracted from I(Ca) during each of 9 subsequent pulses, which loaded the SR. These difference currents reflect I(Ca) inactivation due to SR Ca(2+) release and thus indicate the time course of local [Ca(2+)] in the subsarcolemmal space near Ca(2+) channels produced by SR Ca(2+) release (eg, maximal at 20 ms after the AP activation at 35 degrees C). Furthermore, the rate of change of this difference current may reflect the rate of SR Ca(2+) release as sensed by L-type Ca(2+) channels. These results suggest that peak SR Ca(2+) release occurs within 2.5 or 5 ms of AP upstroke at 35 degrees C and 25 degrees C, respectively. I(Cl(Ca)) might also indicate local [Ca(2+)], and at 35 degrees C in the absence of DIDS (when I(Cl(Ca)) is prominent), peak I(Cl(Ca)) also occurred at a time comparable to the peak I(Ca) difference current. We conclude that SR Ca(2+) release decreases the Ca(2+) influx during the AP by approximately 50% (at both 25 degrees C and 35 degrees C) and that changes in I(Ca) (and I(Cl(Ca))), which depend on SR Ca(2+) release, provide information about local subsarcolemmal [Ca(2+)].

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials*
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism*
  • Heart Ventricles / metabolism
  • Myocardium / metabolism*
  • Rabbits
  • Temperature
  • Ventricular Function*

Substances

  • Calcium Channels
  • Calcium