Mibefradil, an I(Ca,T) blocker, effectively blocks I(Ca,L) in rabbit sinus node cells.

Area of Science:

• Cardiovascular Physiology
• Pharmacology
• Electrophysiology

Background:

• Pacemaker cells in the sinus node control heart rate.
• Calcium (Ca2+) currents play a crucial role in cardiac action potential generation.
• Mibefradil is a known Ca2+ channel blocker with potential effects on heart rate.

Purpose of the Study:

• To investigate if mibefradil slows heart rate by inhibiting T-type Ca2+ current in pacemaker cells.
• To elucidate the specific ionic mechanisms underlying mibefradil's effects on sinus node activity.

Main Methods:

• Isolated rabbit sinus node cells were utilized.
• Patch clamp technique was employed to study action potentials and ionic currents.
• Effects of mibefradil (100 nM and 1 microM) were assessed.

Main Results:

• Mibefradil reduced spontaneous heart rate and action potential amplitude.
• Mibefradil ultimately stopped impulse initiation in sinus node cells.
• Both T-type and L-type Ca2+ currents were significantly inhibited by mibefradil (55% and 64% inhibition, respectively, at 1 microM).
• The observed effects were not attributable to inhibition of the hyperpolarization-activated pacemaker current.

Conclusions:

• Mibefradil slows heart rate through the inhibition of both T-type and L-type Ca2+ currents in pacemaker cells.
• The hypothesis that mibefradil's effect is solely due to T-type Ca2+ current inhibition is not supported.
• Mibefradil exhibits a dual inhibitory action on key calcium currents involved in cardiac pacemaking.