Intracellular Ca2+ release channels include both ryanodine and inositol 1,4,5-triphosphate receptors. They participate in fertilization, neurotransmitter release, hormonal activation, T cell activation, and excitation-contraction (E-C) coupling in muscle. Several modulators and the inhibitors have been well-characterized in terms of their abilities to directly regulate sarcoplasmic reticulum (SR) Ca2+ release channel function. In cardiac muscle, resuming stimulation after a period of rest causes negative or positive inotropic effects in cardiac muscle. They are the rest decay or rest potentiation, respectively. Furthermore, rest decay is due to gradual SR Ca2+ depletion and extrusion from the cell via Na+/Ca2+ exchangeduring rest. Caffeine and ryanodine can both abolish rest potentiation and accelerate rest decay. These actions are attributable directly to increased SR Ca2+ release channel opening and consequent decline of SR Ca2+ content during rest. Bay K 8644 is an L-type Ca2+ channel agonist.
Bay K 8644 increases Ca2+ influx through sarcolemmal Ca2+ channels by increasing the open time of the channel.
In newborn rat ventricular cardiomyocytes, Bay K 8644 (1 μM) treatment increases L-type calcium current density in 2-day-old cells. The higher increase of L-type calcium current density by Bay K 8644 in 2-day- than in 7-day-old cultured cells could be the result of a difference in the phosphorylation level of calcium channels for each stage of development. A one-time dose as low as 10 μg/kg of Bay K 8644 significantly elevates mean arterial pressure (MAP) in endotoxin-treated hypotensive rats. However, It has minimal effects in normal rats. Bay K 8644 also causes a dose-dependent decrease. It shows in heart rate of 37% in endotoxin-treated rats and 39% in control rats.
In summary, Bay K 8644 is a specific L-type Ca2+ channel agonist. Bay K 8644 increases Ca2+ influx through sarcolemmal Ca2+ channels by increasing the open time of the channel.