Potassium channels and human corporeal smooth muscle cell tone: further evidence of the physiological relevance of the Maxi-K channel subtype to the regulation of human corporeal smooth muscle tone in vitro.
OBJECTIVE
Recent evidence indicates that the large conductance, voltage dependent, Ca2+ sensitive K channel or Maxi-K has an important role in the modulation of human corporeal smooth muscle tone and, thus, in erectile capacity. We further clarified the contribution of the Maxi-K channel subtype to the generation of contractile responses in isolated human corporeal tissue strips.


METHODS
We performed pharmacological studies of phenylephrine contracted isolated corporeal tissue strips in the presence and absence of the 2 Maxi-K channel blockers tetraethylammonium chloride (TEA) and charybdotoxin, and the Maxi-K opener NS1619. K channel treatment effects were evaluated using 2 parameters, including 1) the steady state parameter of the empirically determined peak magnitude of the steady state contractile response and 2) the kinetic parameter of time required to achieve half of the peak steady state contractile response or half-time. Electrophysiological studies in freshly isolated and cultured myocytes were performed in parallel to corroborate findings further at the tissue level.


RESULTS
Pre-incubating isolated human corporeal tissue strips with 1 mM. TEA and 1 microM. charybdotoxin was associated with an approximate 20% increase in the peak steady state contractile response and a corresponding approximate 20% decrease in the half-time of the phenylephrine induced contractile response. Conversely, pre-incubation with 10 microM. NS1619 produced a significant, approximately 20% decrease in the peak steady state contractile response and an approximate 38% increase in the half-time of the phenylephrine induced contractile response. Adding 30 to 180 microM. NS1619 to phenylephrine pre-contracted smooth muscle strips resulted in a 30% to 50% reduction in steady state contractile tension. No detectable effect of NS1619 was observed in 120 mM. KCl or 100 mM. TEA pre-contracted corporeal tissue strips. Whole cell recordings of freshly isolated and cultured corporeal myocytes confirmed that 30 microM. NS1619 induced a charybdotoxin sensitive hyperpolarizing current mediated by the Maxi-K channel.


CONCLUSIONS
These in vitro studies confirm and extend previous observations indicating the importance of the Maxi-K channel for regulating human corporeal smooth muscle tone, and by extension, erectile capacity and function.
Spektor
Mariya
M
Department of Urology, Institute for Smooth Muscle Biology, Albert Einstein College of Medicine, Bronx, NY, USA.
Rodriguez
Ramon
R
Rosenbaum
Raymond S
RS
Wang
Hong-Zang
HZ
Melman
Arnold
A
Christ
George J
GJ
D001562:Benzimidazoles / Q000494:pharmacology; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D004594:Electrophysiology; D007172:Erectile Dysfunction / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
D001562:Benzimidazoles; D051036:Large-Conductance Calcium-Activated Potassium Channels; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D018999:Charybdotoxin; C086491:NS 1619; D010656:Phenylephrine; D019789:Tetraethylammonium