Abstract
1. We sought to distinguish two types of Ca$^2+$ channel in guinea-pig
ventricular cells (T-type and L-type) and to characterize their respective
gating and permeation properties when Ca$^2+$ (1-10 mM) is the
charge carrier, as is the case physiologically. 2. Na$^+$ was
removed from both the external and internal solutions to eliminate
currents through Na$^+$ channels and Na$^+$-Ca$^2+$ exchange.
Major differences in the voltage dependence of steady-state inactivation
were exploited to separate the two Ca$^2+$ current components.
3. From a holding potential of -50 mV, only L-type channels were
available to open with depolarization. When holding at -90 mV, T-type
channels contributed an additional rapidly inactivating component
superimposed upon the L-type current. Only the L-type channels thus
identified were sensitive to the dihydropyridine Ca$^2+$ channel
blocker nitrendipine. 4. T-type currents, measured by taking the
difference between the currents elicited from a holding potential
of -90 mV and those elicited from -50 mV, peaked within 10 ms and
decayed completely within 50-100 ms. 5. Macroscopic T-type currents
were largest during depolarizing pulses between -40 and -30 mV (peak
current density of 0.62 +/- 0.21 nA nF-1) and decreased at more positive
potentials, becoming unmeasurably small above 0 mV. 6. Unitary currents
recorded with similar ionic conditions and voltage protocols exhibited
a single-channel conductance of 4-5 pS in 10 mM Ca$^2+$. Ensemble
average currents through a single channel reproduced accurately the
time course of whole-cell T-type current. Permeation properties could
not explain the absence of macroscopic T-type currents at positive
test potentials, which must therefore be attributable to gating.
7. Convolution analysis was employed to clarify the single-channel
basis of the rapidly decaying current waveform of T-type channels.
The latencies to first opening and reopening, which reflect activation
and deactivation, influenced the waveform most strikingly. Open times
were sufficiently brief that they contributed little to shaping the
average current. Thus, macroscopic inactivation largely reflects
rate-limiting activation events. 8. The unitary current amplitudes
and peak open probabilities measured for single T-type channels,
when compared to the average macroscopic T-type current density,
predict 10.6 functional channels per picofarad, or approximately
1700 T-type channels per typical ventricular myocyte.
Description
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Tags
- 1338097
- Animals,
- Calcium
- Calcium,
- Channel
- Channels,
- Factors,
- Female,
- Gating,
- Gov't,
- Guinea
- In
- Ion
- Kinetics,
- Male,
- Membrane
- Myocardium,
- Non-U.S.
- P.H.S.,
- Pigs,
- Potentials,
- Research
- Support,
- Time
- U.S.
- Vitro,