T-type Ca²⁺ current as a trigger for Ca²⁺ release from the sarcoplasmic reticulum in guinea-pig ventricular myocytes

Abstract

1. We have investigated whether Ca²⁺ entry through T-type Ca²⁺ channels participates in triggering Ca²⁺ release from the sarcoplasmic reticulum (SR) in single guinea-pig ventricular myocytes (whole-cell voltage clamp, K₅ fura-2 as [Ca²⁺]_i indicator; all monovalent cations replaced by impermeant ions to record uncontaminated Ca²⁺ currents; T = 23 or 36 °C).

2. T-type Ca²⁺ currents were elicited from a holding potential of -90 mV during steps to -50 to -20 mV. For steps to -50 mV, very small [Ca²⁺]_i transients could be recorded with high loading of the SR (peak Δ[Ca²⁺]_i, 67 ± 41 nM; n = 9).

3. For steps to -40, -30 and -20 mV, we compared the amplitude of Ca²⁺ release for a holding potential of -50 mV with L-type Ca²⁺ current only to Ca²⁺ release for a holding potential of -90 mV with both T- and L-type Ca²⁺ current. Significantly more Ca²⁺ release was observed with T-type current present, and both the T-type current and the additional Ca²⁺ release were suppressed by 50 μM NiCl₂.

4. Ca²⁺ influx through T-type Ca²⁺ channels triggered less Ca²⁺ release than a comparable Ca²⁺ influx through L-type Ca²⁺ channels.

5. Rapid block of T-type Ca²⁺ current during the action potential (50 μM NiCl₂ during steady-state stimulation at 1 or 2 Hz) did not immediately reduce Ca²⁺ release, although a small decrease was observed after longer application.

6. We conclude that T-type Ca²⁺ current can trigger Ca²⁺ release from the SR albeit less efficiently than L-type Ca²⁺ current. T-type current is most likely to provide only a small contribution to the trigger for Ca²⁺ release in normal conditions. These results support the hypothesis that L-type Ca²⁺ channels have a privileged role in excitation-contraction coupling.