T-Type Calcium Current in Latent Pacemaker Cells Isolated from Cat Right Atrium

Whole-cell voltage clamp techniques were used to study Ca2+ currents in latent pacemaker cells isolated from cat right atrium. T-type (ICa,T) and L-type (ICa,L) Ca2+ currents were distinguished by their voltage dependence of activation, and sensitivity to channel blocking agents. In 2.7 mM [Ca]o, ICa,T activation exhibited a voltage threshold of about -50mV and maximum amplitude at -10mV, whereas ICa,L threshold was about -30mV and maximum amplitude was at +10mV. The half-maximal activation voltages of ICa,T was -31.4±0.2mV and ICa,T was -6.2±2.0mV. Overlap of the steady-state activation-inactivation curves for ICa,T showed a "window" current at voltages compatible with the late phase of diastolic depolarization. Maximum ICa,T and ICa,L current densities were 3.3±0.4pA/pF and 12.5±1.3pA/pF, respectively. ICa,T current density in working atrial muscle cells was 0.73±0.31pA/pF. Both ICa,L and ICa,T were blocked by 2mM cobalt. ICa,L but not ICa,T was blocked by 1 μM nifedipine. Nickel (Ni2+: 40 μM) inhibited ICa,T primarily at more negative voltages. In addition, Ni2+ decreased the late phase of diastolic depolarization and significantly increased pacemaker cycle length. These results indicate that latent atrial pacemaker cells exhibit ICa,T that is significantly larger in amplitude than in working atrial muscle cells. ICa,T may contribute current during the late phase of diastolic depolarization. Because latent pacemakers exhibit a more negative maximum diastolic potential, ICa,T may contribute more to latent than to primary pacemaker activity.