Bay K8644 differentiates between potential and receptor operated Ca2+ channels

Area of Science:

• Pharmacology
• Cardiovascular Physiology
• Calcium Channel Modulation

Background:

• Norepinephrine and high potassium (K+) depolarization induce tension in rabbit aorta via calcium influx.
• Bay K8644 is a dihydropyridine known to affect calcium channels.

Purpose of the Study:

• To investigate the specific calcium channels modulated by Bay K8644 in rabbit aorta.
• To compare the effects of Bay K8644 with norepinephrine and high K+ on vascular tension.

Main Methods:

• Isolated rabbit aortic rings were used to measure tension development.
• Vascular tissues were stimulated with norepinephrine and high K+ depolarization.
• The effects of Bay K8644 and the calcium channel antagonist PY108-068 were assessed.

Main Results:

• Bay K8644 increased unidirectional Ca2+ influx and tension in rabbit aorta, even when maximally stimulated by norepinephrine.
• However, Bay K8644 had no effect on tension when arterial rings were maximally activated by high K+ depolarization.
• Tension induced by high K+ and Bay K8644 was more sensitive to the dihydropyridine Ca2+ antagonist PY108-068 than norepinephrine-induced tension.

Conclusions:

• Bay K8644 selectively activates potential-operated calcium channels.
• These channels are distinct from those activated by norepinephrine and are responsive to high K+ depolarization.