Isolated guinea pig coronary smooth muscle cells. Acetylcholine induces hyperpolarization due to sarcoplasmic reticulum calcium release activating potassium channels.

Abstract

Smooth muscle cells, dispersed from the circumflex coronary artery of the guinea pig, were studied with the whole-cell configuration of the patch-clamp. The resting potential of about -40 mV was superimposed by spikelike hyperpolarizations (SLHs) up to -20 mV amplitude. The SLHs resulted from spontaneous transient outward currents (spontaneous TOCs) measured under voltage-clamp (-40 or -50 mV). Acetylcholine (ACh; 10 microM) increased SLHs and TOCs in amplitude and frequency. Atropine blocked the ACh effects. ACh-induced SLHs or TOCs were suppressed by bath application of tetraethylammonium (1 or 10 mM) or by cell dialysis with cesium, suggesting that they result from induction of potassium currents. In cell-attached patches, induction of currents through 130-pS potassium channels was recorded when ACh was bath-applied. An ACh-induced increase in intracellular [Ca2+] is suggested as a second messenger since SHLs and TOCs were suppressed by cell dialysis of 10 mM EGTA. ACh induced SHLs and TOCs in the absence of extracellular calcium. Intracellular application of 5 mg/ml heparin blocked ACh-induced TOCs. When the intracellular calcium stores were depleted by pretreatment with caffeine, the ACh effects were suppressed. Similarly, ACh pretreatment reduced the caffeine-induced outward currents. The results suggested that ACh augments calcium release from the sarcoplasmic reticulum, and the released calcium activates maxi potassium channels. In the single cell, calcium-activated potassium channels generate TOCs and SLHs that sum up to a hyperpolarization of the multicellular tissue.

Ca2+sparks and BK currents in gallbladder myocytes: role in CCK-induced response

“…The Ca 2ϩ spark-activated transient BK current in GBSM caused a transient hyperpolarization up to 37 mV, similar to that described previously for arterial myocytes (18). Taking into account the high frequency of BK currents, even in resting conditions, spontaneous Ca 2ϩ sparks and the resultant hyperpolarizations could decrease GBSM excitability by decreasing the open-state probability of VOCCs.…”

Coactivation of capacitative calcium entry and L-type calcium channels in guinea pig gallbladder

“…The fact that even the fast and small [Ca 2ϩ ] i increases associated with sparks control the plasmalemma voltage (10,24,27) provides a dynamic link between Ca 2ϩ stores and multiple plasma membrane Ca 2ϩ channels. If agonists lead to depletion of Ca 2ϩ stores, it is likely that the resultant focal activation of CCE and L-type Ca 2ϩ channels would replenish the stores and initiate muscle contraction.…”

Effects of noradrenaline on membrane currents and action potential shape in smooth muscle cells from guinea‐pig ureter.

“…It has been reported that internal application of low molecular weight heparin (MW, approximately 6000) effectively inhibits the binding of inositol triphosphate (IP3) to the 'P3-receptor (Ganitkevich & Isenberg, 1990; Komori & Bolton, 1991;Takeda et al 1991). Figure 4 shows the effect of internal application of heparin on the response of Ia to NA.…”